研究者詳細 - 井口　俊博

論文 - 井口　俊博

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Acetic Acid-Indigo Carmine Chromocolonoscopy for Proximal Serrated Lesions: A Randomized, Three-Arm Colonoscopy Study. 国際誌

Hideaki Kinugasa, Sakiko Hiraoka, Sayo Kobayashi, Minoru Matsubara, Teruya Nagahara, Reiji Higashi, Kensuke Takei, Masayasu Ohmori, Takashi Nakamura, Takao Tsuzuki, Shouichi Tanaka, Ryosuke Hirai, Junki Toyosawa, Yuki Aoyama, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Takehiro Tanaka, Toshiharu Mitsuhashi, Motoyuki Otsuka

The American journal of gastroenterology 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Aggressive colorectal cancer (CRC) frequently originates from serrated lesions (SLs), particularly in the proximal colon, which are challenging to detect using standard screening colonoscopy. Although duplicate examinations or chromocolonoscopies are recommended for detecting proximal SLs, evidence from randomized trials is limited. We evaluated the effectiveness of tandem colonoscopy with an acetic acid-indigo carmine mixture (AIM) for detecting SLs in the proximal colon compared to white-light imaging (WLI) and indigo carmine (IC). METHODS: This three-arm, multicenter, randomized controlled trial involving nine institutions enrolled patients undergoing colonoscopy and assigned them randomly to the WLI, IC, or AIM group. The primary outcomes were the SL-detection rate (SDR) of proximal lesions during the second examination (SDR2nd) and SL additional rate (SAR). Secondary outcomes included the detection and additional rates of other polyps, factors contributing to SAR, and complications. RESULTS: Between 2021 and 2024, 1,319 participants with 1,267 polyps were included in the analysis. With AIM, the SDR2nd and SAR were significantly higher compared to WLI or IC (WLI vs. AIM: 2.7% vs. 14.0%, p<.001; IC vs. AIM: 7.9% vs. 14.0%, p=.002, and WLI vs. AIM: 22.4% vs. 69.3%, p<.001; IC vs. AIM: 45.8% vs. 69.3%, p=.001). AIM conferred a higher adenoma-detection rate (ADR)2nd than with WLI (10.5% vs. 24.7%; p<.001) and was an independent factor for SAR (odds ratio [95% confidence interval]: 7.79 [3.76-17.08]). No major adverse events were observed. CONCLUSIONS: AIM significantly improved proximal colon SDRs and outperformed WLI and IC. The relationship between SDR and CRC incidence warrants further investigation.

DOI： 10.14309/ajg.0000000000003411

Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn's disease activity in the small bowel.

Muneyori Okita, Kento Takenaka, Fumihito Hirai, Shinya Ashizuka, Hideki Iijima, Shigeki Bamba, Toshimitsu Fujii, Kenji Watanabe, Yosuke Shimodaira, Hisashi Shiga, Sakiko Hiraoka, Toshihiro Inokuchi, Takeshi Yamamura, Ryo Emoto, Shigeyuki Matsui

Journal of gastroenterology 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Small bowel (SB) lesions in Crohn's disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB. METHODS: This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%. RESULTS: Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67-0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65-0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1). CONCLUSION: LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility.

DOI： 10.1007/s00535-025-02223-1

Changes of leucine-rich alpha 2 glycoprotein could be a marker of changes of endoscopic and histologic activity of ulcerative colitis. 国際誌

Yuki Aoyama, Sakiko Hiraoka, Eriko Yasutomi, Toshihiro Inokuchi, Takehiro Tanaka, Kensuke Takei, Shoko Igawa, Keiko Takeuchi, Masahiro Takahara, Junki Toyosawa, Yasushi Yamasaki, Hideaki Kinugasa, Jun Kato, Hiroyuki Okada, Motoyuki Otsuka

Scientific reports 15 ( 1 ) 5248 - 5248 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Leucine-rich alpha 2 glycoprotein (LRG) is one of the serum biomarkers for disease activity of ulcerative colitis (UC). We focused on the correlation between the changes of LRG and the changes of endoscopic and histologic activity of UC, in comparison to the changes of fecal calprotectin (Fcal), fecal immunochemical test (FIT), and C-reactive protein (CRP). Seventy-nine patients with two or more colonoscopies were enrolled, and 123 paired colonoscopies and 121 paired biopsies were examined. With regard to the change of endoscopic/histologic activity between the preceding and subsequent colonoscopy, there was improvement (n = 29/45), unchanging (n = 63/36), and worsening (n = 31/40). The correlations between the changes of marker levels and endoscopic/histologic activity were Fcal; r = 0.50/0.39 and FIT; r = 0.41/0.40, LRG; r = 0.42/0.40 and CRP; r = 0.22/0.17. Furthermore, when the correlation between the changes of LRG levels and the changes of endoscopic/histological activity was compared with those of other markers, the correlation of LRG tended to be superior to those of CRP (CRP vs. LRG; p = 0.08/0.01). LRG is equivalent to fecal markers and superior to CRP, when inferring changes in disease activity of UC based on changes in its level.

DOI： 10.1038/s41598-025-89615-8

Short- and longer-term learning effects from virtual scale endoscopy videos: a useful tool for colorectal lesion size estimation (with video). 国際誌

Ryosuke Hirai, Hideaki Kinugasa, Mikako Ishiguro, Junki Toyosawa, Yuki Aoyama, Shoko Igawa, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Seiji Kawano, Sakiko Hiraoka, Motoyuki Otsuka

Gastrointestinal endoscopy 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIMS: Accurate assessment of colorectal polyp size is crucial for determining treatment and surveillance policies. However, visual estimation of lesion diameter is often inaccurate, making simple and effective educational tools essential. We aimed to evaluate the learning effects of virtual scale endoscopy (VSE). METHODS: Thirty-three endoscopists first watched pre-learning videos for SET1. They then estimated the diameters of 20 lesions and referred to instructional videos with VSE for self-study. Subsequently, they watched the post-learning videos for SET2 and estimated the lesion diameters. The error between the estimated and correct lesion sizes of both sets was compared. To evaluate longer-term learning effects, participants answered SET3 and SET4, which consisted of the same questions as SET2 and SET1, respectively, 2-3 months later without watching the instructional video for SET2. RESULTS: The error in the participants' estimation of the correct lesion diameter improved from SET1 to SET2 (34.7 mm ± 6.6 vs. 30.7 mm ± 7.7; p = 0.048), with a significant learning effect and error improvement specifically among non-experts (35.2 mm ± 5.3 vs. 30 mm ± 6.8; p = 0.028). In the SET3 and SET4, participants' errors indicated that the learning effect was well maintained (SET2 vs. SET3; 30.7 mm ± 7.7 vs. 28.6 mm ± 7.2; p = 0.1, and SET1 and SET4: 34.7 mm ± 6.6 vs. 31.7 mm ± 7.1; p = 0.025). CONCLUSIONS: VSE videos are a valuable learning tool for estimating lesion diameter, particularly for novice endoscopists, both in the short- and longer-term.

DOI： 10.1016/j.gie.2024.10.038

増大号炎症性腸疾患2024 主題炎症性腸疾患の内科治療基本治療薬(5-ASA製剤,副腎皮質ステロイド,チオプリン製剤)

平岡佐規子, 石黒美佳子, 豊澤惇希, 青山祐樹, 井川翔子, 竹内桂子, 山崎泰史, 井口俊博, 衣笠秀明, 髙原政宏, 大塚基之, 金谷信彦, 近藤喜太, 田中健大

胃と腸 59 ( 10 ) 1453 - 1461 2024年10月

Endoscopic lavage for an infected pelvic hematoma in a patient with pelvic sepsis after anterior pelvic exenteration.

Ryohei Shoji, Fuminori Teraishi, Yoshitaka Kondo, Toshihiro Inokuchi, Hideaki Kinugasa, Toshiyoshi Fujiwara

Asian journal of endoscopic surgery 17 ( 4 ) e13384 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Anastomotic leakage and subsequent pelvic sepsis are serious complications after surgery for pelvic malignancies, particularly challenging due to the large pelvic cavity dead space post-exenteration. We report a 47-year-old man treated for a severely infected pelvic hematoma and sepsis following anastomotic leakage after anterior pelvic exenteration. Post robot-assisted exenteration for locally advanced sigmoid colon cancer treated with neoadjuvant chemotherapy, a pelvic abscess from anastomotic dehiscence was identified. Initial CT-guided drainage and subsequent laparoscopic drainage were performed. On postoperative day 22, a bleeding left internal iliac pseudoaneurysm required embolization. Despite these efforts, the sepsis worsened due to an enlarged, infected hematoma. Endoscopic lavage, in collaboration with skilled endoscopists, successfully removed the hematoma, leading to an improved inflammatory response, and the patient was discharged. Endoscopic lavage proved to be the safest and most effective treatment for pelvic sepsis with an infected hematoma after various attempted interventions.

DOI： 10.1111/ases.13384

Adverse events after different endoscopic resection procedures for small and intermediate-sized colorectal polyps. 国際誌

Junki Toyosawa, Yasushi Yamasaki, Yuki Aoyama, Kensuke Takei, Shoko Igawa, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Sakiko Hiraoka, Hiroyuki Okada, Motoyuki Otsuka

Digestive diseases (Basel, Switzerland) 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) and underwater endoscopic mucosal resection (UEMR) have been developed recently, in addition to conventional methods, but adverse events of each method have not been fully clarified. We compared outcomes of each method for the appropriate choice. PATIENTS AND METHODS: Patients who underwent CSP, endoscopic mucosal resection (EMR)/hot snare polypectomy (HSP) or UEMR for small and intermediate-sized colorectal polyps between April 2017 and June 2020 were retrospectively examined. The rate of adverse events and recurrences due to each method were determined as main outcomes. Clinical factors related with adverse events were examined. RESULTS: A total of 1,025 patients with 3,163 polyps underwent polypectomy using any of the methods. CSP, EMR/HSP and UEMR were performed for 704 (22.2%), 2,145 (67.8%) and 314 polyps (9.9%), and median size for each method was 4, 6 and 7 mm, respectively. Delayed bleeding for CSP, EMR/HSP and UEMR was 0%, 0.2% and 0.6% (P = 0.15), and perforation was 0%, 0.1% and 0%, respectively (P = 0.62). Recurrence after CSP, EMR/HSP and UEMR was 0.1%, 0.04% and 1.0%, respectively (P < 0.01). Recurrence for UEMR was significantly higher in the early stage of procedure introduction (P = 0.001). Oral anticoagulants were the risk factor for delayed bleeding (P < 0.01, respectively). CONCLUSIONS: There was no significant difference regarding adverse events among each method for small and intermediate-sized polyps, although recurrence rate after UEMR was higher than other methods.

DOI： 10.1159/000540365

Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation. 国際誌

Masaya Iwamuro, Daisuke Ennishi, Nobuharu Fujii, Ken-Ichi Matsuoka, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Motoyuki Otsuka

BMC gastroenterology 24 ( 1 ) 140 - 140 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM. METHODS: This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated. RESULTS: The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%. CONCLUSIONS: This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.

DOI： 10.1186/s12876-024-03221-y

消化管の炎症を診るクローン病小腸病変評価における経腹超音波検査の有用性

高原政宏, 平岡佐規子, 青山祐樹, 井川翔子, 井口俊博, 大西秀樹, 大塚基之

超音波医学 51 ( Suppl. ) S187 - S187 2024年4月

UnderwaterとUnder-gelでの大腸腫瘍性病変に対する境界診断能の検討

豊澤惇希, 山崎泰史, 青山祐樹, 井川翔子, 井口俊博, 衣笠秀明, 高原政宏, 平岡佐規子, 大塚基之

Gastroenterological Endoscopy 66 ( Suppl.1 ) 969 - 969 2024年4月

Utility of Combined Use of Transabdominal Ultrasonography and Fecal Immunochemical Test Examinations in Ulcerative Colitis.

Masahiro Takahara, Sakiko Hiraoka, Masayasu Ohmori, Keiko Takeuchi, Kensuke Takei, Yuki Aoyama, Eriko Yasutomi, Shoko Igawa, Toshihiro Inokuchi, Junki Toyosawa, Yasushi Yamasaki, Hideaki Kinugasa, Keita Harada, Hideki Onishi, Hiroyuki Okada

Acta medica Okayama 78 ( 1 ) 79 - 83 2024年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study examined the utility of the combined use of transabdominal ultrasonography (TUS) and fecal immunochemical testing (FIT) to detect mucosal inflammation, vis-a-vis the Mayo endoscopic subscore (MES), in ulcerative colitis (UC). Sixty-three UC patients who underwent TUS and FIT were retrospectively enrolled. For TUS, the colon was divided into five segments, and the bowel wall thickness was measured and evaluated. The accuracy of FIT (> 100 ng/ml) in detecting mucosal inflammation (MES>0) was 0.93, whereas that of TUS (BWT>2 mm) in each segment was 0.84-0.97. The combined use of TUS and FIT may be helpful in noninvasive treatment strategies.

DOI： 10.18926/AMO/66674

小腸疾患治療の最前線小腸疾患を有する先天性心疾患患者における治療の現状と問題点

亀高大介, 川野誠司, 河野吉泰, 井口俊博, 平岡佐規子

日本消化管学会雑誌 8 ( Suppl. ) 207 - 207 2024年1月

Colorectal Ganglioneuromas Associated with Cowden Syndrome

Toshiki Ozato, Yasushi Yamasaki, Toshihiro Inokuchi, Motoyuki Otsuka

Internal Medicine 2024年

大腸神経節細胞腫により診断に至ったCowden症候群の1例

本田真奈美, 山崎泰史, 豊澤惇希, 井口俊博, 衣笠秀明, 高原政宏, 田中健大, 平岡佐規子, 大塚基之

日本消化器病学会中国支部例会・日本消化器内視鏡学会中国支部例会プログラム・抄録集 120回・131回 68 - 68 2023年11月

Low Patient Weight and Long Intubation Time Are Key Factors for Pain during Colonoscopy.

Shohei Oka, Keita Harada, Shumpei Yamamoto, Eriko Yasutomi, Shoko Igawa, Masayasu Ohmori, Mami Hirai, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Sakiko Hiraoka, Hiroyuki Okada

Acta medica Okayama 77 ( 5 ) 471 - 478 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although the clinical usefulness of colonoscopy has been established, the procedure remains painful for many patients. This study was designed to clarify the factors predicting colonoscopy-related pain. We evaluated 283 consecutive patients who completed a first-ever, total colonoscopy without sedatives or analgesics. The severity of pain symptoms was evaluated by a numeric rating scale (NRS) in a questionnaire immediately after the colonoscopy. Patient backgrounds and endoscopic findings were analyzed to evaluate their association with pain. Out of 283 patients, 53 scored their pain 0-1 on the NRS while 48 scored it 6-10. We defined the colonoscopies of the former and latter patients as painless and painful, respectively, and compared the two. Multivariate analyses revealed that low body weight (OR 4.95, 95%CI 1.89-12.99) and longer intubation time (OR 3.63, 95%CI 1.46-9.03) were significant risk factors for painful colonoscopy. To identify factors contributing to the increased intubation time, we divided subjects into short- and long-intubation-time groups based on a median insertion time of 7 min. Older age (OR 2.28, 95%CI 1.31-3.98), previous abdominal surgery (OR 1.93, 95%CI 1.13-3.32) and findings of invasive cancer (OR 10.90, 95%CI 1.34-88.90) were significant factors for longer intubation time.

DOI： 10.18926/AMO/65969

IBD診療におけるtreat to targetを考える Treat to targetを意識したクローン病におけるsurrogate markerの組み合わせ

井口俊博, 平岡佐規子, 青山祐樹, 竹井健介, 井川翔子, 高原政宏, 大塚基之

日本大腸肛門病学会雑誌 76 ( 9 ) A51 - A51 2023年9月

IBD診療におけるtreat to targetを考える Treat to targetを意識したクローン病におけるsurrogate markerの組み合わせ

井口俊博, 平岡佐規子, 青山祐樹, 竹井健介, 井川翔子, 高原政宏, 大塚基之

日本大腸肛門病学会雑誌 76 ( 9 ) A51 - A51 2023年9月

Paroxysmal nocturnal hemoglobinuria with ulcerative colitis. 国際誌

Kenta Hayashino, Yuki Fujiwara, Yuki Isokane, Haruna Tobita, Tomoko Inomata, Toshihiro Inokuchi, Takeru Asano, Shiro Kubonishi, Masahiro Takatani, Yasushi Hiramatsu

Annals of hematology 102 ( 9 ) 2625 - 2626 2023年9月

Predictive Factors for Efficacy of Oral Tacrolimus Induction Therapy in Moderate to Severe Ulcerative Colitis Patients: Large Multicenter Retrospective Cohort Study. 国際誌

Naoki Oshima, Sakiko Hiraoka, Ryohei Hayashi, Sakuma Takahashi, Manabu Ishii, Shinichi Hashimoto, Kazuo Yashima, Shoko Igawa, Toshihiro Inokuchi, Yoshitaka Ueno, Tomoki Inaba, Hiroshi Matsumoto, Kousaku Kawashima, Taro Takami, Hajime Isomoto, Akiko Shiotani, Shinji Tanaka, Shunji Ishihara

Inflammatory bowel diseases 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Tacrolimus (TAC), a calcineurin inhibitor, is used for remission induction therapy in patients with moderate to severe ulcerative colitis (UC), with short-term efficacy and related predictive factors shown in previous cohort studies. However, most studies reported data for only a limited number of patients enrolled from a single center. We performed a large multicenter retrospective cohort study to identify factors related to prediction of clinical remission in UC patients treated with oral TAC. METHODS: The medical records of patients with moderate to severe UC treated with oral TAC as induction therapy at 7 institutions between April 2009 and March 2017 were retrospectively reviewed. RESULTS: A total of 216 patients who received TAC for induction were analyzed, of whom 123 (56.9%) showed clinical remission at week 12. Logistic regression analysis indicated that previous or current use of antitumor necrosis factor (TNF)-α antibodies (odds ratio [OR], 0.259; P = .006), and concomitant treatment with 5-aminosalicylate (5-ASA) at the baseline (OR, 0.268; P = .005) were independent predictive factors correlated with failure of clinical remission, whereas higher levels of C-reactive protein (OR, 1.124; P = .014) predicted achievement of clinical remission. CONCLUSIONS: Results of this multicenter study clearly indicate the efficacy of TAC induction therapy for patients with moderate to severe UC. Notably, previous or current use of anti-TNF-α antibodies was associated with poor achievement of clinical remission by week 12.

DOI： 10.1093/ibd/izad150

血流豊富な粘膜下腫瘍の形態を呈した上行結腸血管周囲類上皮細胞腫の1例

青山祐樹, 井口俊博, 平岡佐規子, 豊澤惇希, 竹井健介, 井川翔子, 山崎泰史, 衣笠秀明, 高原政宏, 庄司良平, 近藤喜太, 柳井広之, 大塚基之

日本消化器内視鏡学会中国支部例会 130回 81 - 81 2023年6月

炎症性腸疾患の内視鏡的モニタリング(下部) 潰瘍性大腸炎においてLeucine-rich alpha 2 glycoprotein(LRG)は内視鏡的および組織学的活動性の変化の予測に有用である

青山祐樹, 井口俊博, 平岡佐規子

Gastroenterological Endoscopy 65 ( Suppl.1 ) 728 - 728 2023年4月

【あなたの知らないIBD診療の世界】新規治療法・検査法 IBDに対するバイオマーカーの使い方血中マーカーと便中マーカー

井口俊博, 平岡佐規子, 青山祐樹, 竹井健介, 井川翔子, 高原政宏

臨床消化器内科 38 ( 4 ) 422 - 428 2023年3月

記述言語：日本語出版者・発行元：(株)日本メディカルセンター

＜文献概要＞潰瘍性大腸炎およびクローン病を含む炎症性腸疾患(IBD)は,単なる症状の改善にとどまらず,内視鏡的な治癒を目指すことにより予後が改善することが証明されている.したがって内視鏡的活動性の把握が重要であり,内視鏡重症度の代替マーカーである,血中,便中マーカーをそれぞれ上手に使いこなすことが肝要である.一方で各マーカーの注意点があり,血中マーカーではCRPだけでなく,近年LRGが利用可能となり,実臨床での活用が期待される.また便中マーカーはとくに疾患活動性が落ちてきたステージでの利用がより有用であり,内視鏡的寛解の判断に強みをもつ.IBD診療においては,各マーカーの長所,注意点に習熟し,より良いモニタリングを行うことが求められる.

Usefulness of Intestinal Ultrasound to Detect Small Intestinal Stenosis in Patients With Crohn's Disease. 国際誌

Keiko Takeuchi, Toshihiro Inokuchi, Masahiro Takahara, Masayasu Ohmori, Eriko Yasutomi, Shohei Oka, Shoko Igawa, Kensuke Takei, Yuki Baba, Seiji Kawano, Yasushi Yamasaki, Hideaki Kinugasa, Keita Harada, Sakiko Hiraoka, Hiroyuki Okada

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 42 ( 2 ) 373 - 383 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Double balloon enteroscopy (DBE) with retrograde contrast is useful as a monitoring tool for small intestinal lesions in Crohn's disease (CD), but these are burdensome for patients. Intestinal ultrasound (IUS) can be used with ease in daily clinical practice, but there is less evidence regarding the accuracy of detection of small intestinal stenosis in CD. This study aimed to examine the diagnostic power of IUS for small intestinal stenosis in patients with CD. METHODS: The findings of DBE and IUS in 86 patients with CD with small intestinal lesions were evaluated. Using DBE as the reference standard, we examined the detection rate of IUS for small intestinal stenosis. We evaluated three parameters: luminal narrowing, prestenotic dilation, and to-and-fro movement for determining stenosis using IUS. In addition, we compared the characteristics between the stenosis-detectable and stenosis-undetectable groups by IUS. RESULTS: Of the 86 patients, 30 had small intestinal stenosis. In IUS findings, when lesions that met two or more of the three parameters were judged as stenosis, the detection rate was 70.0% for sensitivity, 98.2% for specificity, and 88.4% for accuracy. Moreover, there were patients with a younger age at diagnosis (P < 0.05) and more ileocolonic disease location (P < 0.05) in the stenosis-detectable group by IUS. The stenoses detected by IUS were significantly longer than those undetected by IUS (14.1 mm versus 5.2 mm, P < 0.05). CONCLUSIONS: IUS delivered reliable results for clinically important small intestinal stenosis of CD with high diagnostic accuracy.

DOI： 10.1002/jum.16038

RNA editing is a valuable biomarker for predicting carcinogenesis in ulcerative colitis. 国際誌

Kazutaka Takahashi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Kazuyoshi Gotoh, Shuya Yano, Yuzo Umeda, Toshihiro Inokuchi, Caiming Xu, Kazuhiro Yoshida, Hibiki Umeda, Toshiaki Takahashi, Sho Takeda, Ryuichi Yoshida, Fuminori Teraishi, Hiroyuki Kishimoto, Yoshiko Mori, Kazuhiro Noma, Yoshinaga Okugawa, Sakiko Hiraoka, Hiroyuki Michiue, Hiroshi Tazawa, Osamu Matsushita, Ajay Goel, Toshiyoshi Fujiwara

Journal of Crohn's & colitis 17 ( 5 ) 754 - 766 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIMS: Ulcerative colitis (UC) can develop colitis-associated colorectal neoplasm (CAN). Adenine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA (ADAR), induces the posttranscriptional modification of critical oncogenes, including antizyme inhibitor 1 (AZIN1), leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. METHODS: We systematically analyzed a cohort of 139 UC cases (40 acute phase, 73 remission phase, 26 CAN). The degree of inflammation was evaluated using the Mayo endoscopic score (MES). RESULTS: The type 1 IFN-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN, and tumor site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was down-regulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC. CONCLUSIONS: The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

DOI： 10.1093/ecco-jcc/jjac186

【IBDの既存治療を最新の知見から見直す!】IBDの5-ASA製剤による治療を見直す

高原政宏, 平岡佐規子, 井口俊博

IBD Research 16 ( 4 ) 219 - 224 2022年12月

記述言語：日本語出版者・発行元：(株)先端医学社

5-アミノサリチル酸(5-ASA)製剤は,安全性が高く,使用しやすい薬剤であり,炎症性腸疾患(IBD),とくに潰瘍性大腸炎においては,軽症～中等症の治療薬の第一選択薬として,寛解導入から寛解維持まで広く用いられている.わが国では,現在使用できる5-ASA製剤は4種類あり,各薬剤の特徴を理解したうえで,病勢や患者の状況に合わせて薬剤の選択をしていく.IBD患者の増加に伴い,5-ASA製剤の使用頻度は今後,さらに増していくであろう一方で,近年は5-ASA製剤の不耐症例も増加している.不耐の特徴や対処法に関する知識も必要とされ,適切な対応を取ることも求められている.(著者抄録)

【高齢者潰瘍性大腸炎の現状】高齢者潰瘍性大腸炎の内科的治療とその見極め

井口俊博, 高原政宏, 平岡佐規子

日本消化器病学会雑誌 119 ( 11 ) 992 - 1003 2022年11月

記述言語：日本語出版者・発行元：(一財)日本消化器病学会

近年,高齢潰瘍性大腸炎(UC)患者数が増加しており,特に若年発症して長期経過を追っている高齢UC症例と異なり,高齢になって新規に発症したUCは治療に難渋する症例が少なくない.また年齢だけで高齢者の全身状態を判断することはできず,症例によって脆弱性やリスクが異なるため,注意が必要である.現在使用できる治療薬はいずれも高齢者を対象とした試験を経ず保険収載されており,リアルワールドデータを基に有効性,安全性の判断をせざるを得ない.高齢者特有の併存疾患の管理,ポリファーマシーと相互作用,認知症,身体機能低下,易感染状態などのリスクを考慮し,重篤な状態になる前に常に早期介入を心掛ける必要がある.(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01118&link_issn=&doc_id=20221116250003&doc_link_id=%2Fck8syokb%2F2022%2F011911%2F003%2F0992-1003%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fck8syokb%2F2022%2F011911%2F003%2F0992-1003%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

クローン病患者の内視鏡活動性と活動性の変化を予測するバイオマーカーは?

井口俊博, 平岡佐規子, 豊澤惇希, 竹井健介, 青山祐樹, 井川翔子, 竹内桂子, 山崎泰史, 衣笠秀明, 高原政宏, 原田馨太, 岡田裕之

日本消化器病学会雑誌 119 ( 臨増大会 ) A750 - A750 2022年10月

手技の解説クローン病におけるダブルバルーン内視鏡下逆行性造影の実際

井口俊博, 川野誠司, 平岡佐規子

Gastroenterological Endoscopy 64 ( 10 ) 2308 - 2316 2022年10月

記述言語：日本語出版者・発行元：(一社)日本消化器内視鏡学会

クローン病患者の7割以上が小腸病変を有するとされ,小腸病変のモニタリングとその制御は患者のQOLに直結する.従ってクローン病診療では,全小腸を高精度でかつ手軽に,そして低侵襲にモニタリングすることが求められるが,残念ながらすべてを兼ね備えた検査やマーカーは未だ存在しない.ダブルバルーン内視鏡検査は,クローン病小腸病変に対するモニタリング検査の1つとして,また時に内視鏡的拡張術目的に広く使用されている.当科ではダブルバルーン内視鏡検査の際に通常の観察に加えて先端バルーンを拡張させて逆行性造影を行い,それまでは難しかった深部小腸の評価をルーチンで行っている.本稿では,クローン病小腸病変に対するダブルバルーン内視鏡下逆行性造影の手順やコツを解説する.(著者抄録)

The Colon Wall Thickness Measured Using Transabdominal Ultrasonography Is Useful for Detecting Mucosal Inflammation in Ulcerative Colitis.

Masahiro Takahara, Sakiko Hiraoka, Masayasu Ohmori, Keiko Takeuchi, Kensuke Takei, Eriko Yasutomi, Shoko Igawa, Shumpei Yamamoto, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Keita Harada, Hideki Ohnishi, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 61 ( 18 ) 2703 - 2709 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective Transabdominal ultrasonography (TUS) is a non-invasive procedure that is reportedly useful for managing ulcerative colitis (UC) and assessing bowel wall thickness (BWT), the most common measure of mucosal inflammation. However, the exact range of BWT that reflects disease activity remains undetermined. The present study clarified the BWT due to disease activity by comparing the use of TUS in each segment of the colon versus using colonoscopy (CS) and determined the usefulness of TUS in patients with UC. Methods We divided the colon into five segments and measured the BWT using TUS. The results were then compared to the Mayo endoscopic subscore (MES) classification to determine the accuracy of BWT measurement. Patients Eighty patients with UC who underwent TUS within 14 days of CS were retrospectively registered. Results We evaluated a total of 268 images depicting each segment among 80 patients with UC. The BWT was positively correlated with endoscopic activity (0.69, p<0.0001). In each segment, the relationship between a BWT>2 mm and an MES>0 had the highest sensitivity, specificity, and accuracy (0.85-1.00, 0.67-0.92, and 0.81-0.97, respectively). Conclusion This study concluded that TUS was a useful method of detecting an MES>0, which indicates the presence of inflammation and its location among UC patients. MES>0 was found to be highly accurate when a BWT>2 mm was considered positive. This non-invasive method may help control disease activity in patients with UC.

DOI： 10.2169/internalmedicine.8827-21

人工肛門造設状態で帝王切開による分娩が可能であった難治性クローン病の一例

安富有希, 井川翔子, 青山祐樹, 竹井健介, 安富絵里子, 井口俊博, 高原政宏, 平岡佐規子, 岡田裕之, 近藤喜太

日本消化器病学会中国支部例会プログラム・抄録集 117回 69 - 69 2022年6月

Fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection for patients with immunosuppressants and steroids. 国際誌

Shumpei Yamamoto, Hideaki Kinugasa, Yasushi Yamasaki, Mami Hirai, Soichiro Ako, Kensuke Takei, Shoko Igawa, Eriko Yasutomi, Shohei Oka, Masayasu Ohmori, Toshihiro Inokuchi, Keita Harada, Sakiko Hiraoka, Kazuhiro Nouso, Takehiro Tanaka, Hiroyuki Okada

DEN open 2 ( 1 ) e83 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Transient fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD) remain a challenge. The aim of this study was to assess the risk factors of post-ESD fever and post-ESD coagulation syndrome (PECS), focusing on the involvement of immunosuppressive drugs and steroids (IM). METHODS: This retrospective analysis included 510 patients who underwent colorectal ESD at Okayama University Hospital from 2015 to 2020. The incidence rate, clinical outcome, and factors associated with post-ESD fever and PECS were investigated. RESULTS: Post-ESD fever and PECS occurred in 63 patients (12.4%) and 43 patients (8.4%), respectively. In multivariate analysis, the American Society of Anesthesiologists Physical Status ≥3, the use of immunosuppressants or prednisolone ≥5mg (IM group), and injury to muscle layer/perforation were significantly associated with post-ESD fever. In PECS, IM group, tumors located on the right side, treatment time ≥60 min, injury to the muscle layer, and multiple lesions were independent risk factors. Both post-ESD fever and PECS improved conservatively in the IM group, and no serious complication was observed. CONCLUSIONS: The use of IM was a risk factor for both post-ESD fever and PECS. However, there were no serious complications in colorectal ESD for patients taking IM.

DOI： 10.1002/deo2.83

Metformin ameliorates chronic colitis in a mouse model by regulating interferon-γ-producing lamina propria CD4+ T cells through AMPK activation. 国際誌

Masahiro Takahara, Akinobu Takaki, Sakiko Hiraoka, Kensuke Takei, Eriko Yasutomi, Shoko Igawa, Shumpei Yamamoto, Shohei Oka, Masayasu Ohmori, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Keita Harada, Heiichiro Udono, Hiroyuki Okada

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 ( 2 ) e22139 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Metformin, a commonly prescribed drug for type 2 diabetes mellitus, has been shown to activate AMP-activated protein kinase (AMPK). Notably, AMPK activation has recently been observed to be associated with anti-inflammatory responses. Metformin is also reported to elicit anti-inflammatory responses in CD4+ T cells, resulting in improvement in experimental chronic inflammatory diseases, such as systemic lupus erythematosus. To investigate the effect of metformin on inflammatory bowel disease (IBD), we developed a T cell-transfer model of chronic colitis in which SCID mice were injected with CD4+ CD45RBhigh T cells to induce colitis. We examined the effects of metformin via in vitro and in vivo experiments on lamina propria (LP) CD4+ T cells. We observed that metformin suppresses the frequency of interferon (IFN) -γ-producing LP CD4+ T cells in vitro, which were regulated by AMPK activation, a process possibly induced by the inhibition of oxidative phosphorylation. Furthermore, we examined the effects of metformin on an in vivo IBD model. Metformin-treated mice showed AMPK activation in LP CD4+ T cells and ameliorated colitis. Our study demonstrates that metformin-induced AMPK activation in mucosal CD4+ T cells contributes to the improvement of IBD by suppressing IFN-γ production. Moreover, our results indicate that AMPK may be a target molecule for the regulation of mucosal immunity and inflammation. Thus, AMPK-activating drugs such as metformin may be potential therapeutic agents for the treatment of IBD.

DOI： 10.1096/fj.202100831RR

Enriched CD45RA-CD62L+ central memory T and decreased CD3+CD56+ natural killer T lymphocyte subsets in the rectum of ulcerative colitis patients. 国際誌

Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada

International journal of immunopathology and pharmacology 36 20587384211051982 - 20587384211051982 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: To investigate the distinctive features of lymphocytes promoting inflammation in ulcerative colitis. METHODS: We performed flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and colorectal mucosa lymphocytes in ulcerative colitis patients (n = 13) and control patients (n = 5). RESULTS: CD62L+/CD3+CD4+ (35.7 ± 14.0% vs. 19.9 ± 6.4%) and CD62L+/CD3+CD4- cells (17.1 ± 17.4% vs. 2.4 ± 3.9%) were higher in the rectum of ulcerative colitis patients than in control patients. Subpopulation analysis revealed that CD45RA-CD62L+/CD3+CD4+, that is, central memory T cell fraction in CD4+ T cells, was significantly increased in the rectum of ulcerative colitis, compared to that in control patients (23.3 ± 10.5% vs. 8.2 ± 4.0%). Comparison of rectum and colon samples in ulcerative colitis patients indicated that CD56+/CD3+ was decreased in the rectum compared to that in the colon (11.3 ± 12.5% vs. 21.3 ± 16.5%). The ratio of CD56+/CD3+ was also decreased in the rectum of active ulcerative colitis patients compared to that in ulcerative colitis patients at the endoscopic remission stages (2.8 ± 1.7% vs. 18.5 ± 13.3%). CONCLUSION: We demonstrated that CD62L+ T lymphocytes, particularly the CD45RA-CD62L+ T cell subset that represents central memory T cells, were increased in the rectum of patients with ulcerative colitis. In addition, the CD56+/CD3+ subset (natural killer T cells) was decreased in the rectum compared to that of less inflamed colonic mucosa. These results suggest that the enrichment of central memory T lymphocytes and the reduction of natural killer T cells in the gut mucosa are involved in the pathogenesis of ulcerative colitis.

DOI： 10.1177/20587384211051982

高齢者潰瘍性大腸炎の内科的治療とその見極め

井口俊博, 高原政宏, 平岡佐規子

日本消化器病学会雑誌(Web) 119 ( 11 ) 992 - 1003 2022年

Evaluation of complete cold forceps polypectomy resection rate for 3- to 5-mm colorectal polyps. 国際誌

Yasushi Yamasaki, Keita Harada, Shumpei Yamamoto, Eriko Yasutomi, Mami Hirai, Masayasu Ohmori, Shohei Oka, Toshihiro Inokuchi, Hideaki Kinugasa, Yuusaku Sugihara, Masahiro Takahara, Sakiko Hiraoka, Takehiro Tanaka, Toshiharu Mitsuhashi, Hiroyuki Okada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 33 ( 6 ) 948 - 954 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND STUDY AIMS: The propriety of cold forceps polypectomy (CFP) using jumbo biopsy forceps for diminutive polyps remains controversial. We conducted a prospective study to evaluate the complete CFP resection rate of 3-5-mm polyps using additional endoscopic mucosal resection (EMR) specimens following CFP. PATIENTS AND METHODS: Patients with 3-5-mm protruded or flat elevated colorectal polyps diagnosed endoscopically as adenomas or serrated lesions were prospectively enrolled. CFP using jumbo biopsy forceps was used to remove the eligible polyps and repeated until the absence of residuals were confirmed via image-enhanced endoscopy or chromoendoscopy. After CFP, saline was injected at the defect, and the marginal specimen of the defect was resected using EMR to histologically evaluate the residue. The primary outcome was the complete CFP resection rate, which was defined as no residue at the EMR site. Other outcomes were the number of CFP bites and the complete resection rate by lesion size. RESULTS: Eighty patients with 120 polyps were enrolled. The mean polyp size was 4.1 ± 0.7 mm. The overall complete resection rate was 96.7% (95% confidence interval [CI], 91.7-98.7), and the rates for 3-, 4- and 5-mm polyps were 100% (95% CI, 86.7-100), 96.0% (95% CI, 86.5-98.9) and 95.5% (95% CI, 85.1-98.8), respectively. The one-bite CFP rates were 92%, 60% and 31% for the 3-, 4- and 5-mm polyps, respectively. CONCLUSIONS: The complete CFP resection rate for 3-5-mm polyps was acceptable, although the one-bite clearance rate decreased as the polyp size increased (UMIN000028841).

DOI： 10.1111/den.13895

Heterogeneous distribution of Fusobacterium nucleatum in the progression of colorectal cancer. 国際誌

Shumpei Yamamoto, Hideaki Kinugasa, Mami Hirai, Hiroyuki Terasawa, Eriko Yasutomi, Shohei Oka, Masayasu Ohmori, Yasushi Yamasaki, Toshihiro Inokuchi, Keita Harada, Sakiko Hiraoka, Kazuhiro Nouso, Takehiro Tanaka, Fuminori Teraishi, Toshiyoshi Fujiwara, Hiroyuki Okada

Journal of gastroenterology and hepatology 36 ( 7 ) 1869 - 1876 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Fusobacterium nucleatum (Fn) is involved in colorectal cancer (CRC) growth and is a biomarker for patient prognosis and management. However, the ecology of Fn in CRC and the distribution of intratumoral Fn are unknown. METHODS: We evaluated Fn and the status of KRAS and BRAF in 200 colorectal neoplasms (118 adenomas and 82 cancers) and 149 matched adjacent normal mucosas. The differentiation status between "surface" and "deep" areas of cancer tissue and matched normal mucosa were analyzed in 46 surgical samples; the Ki-67 index was also evaluated in these samples. RESULTS: Fusobacterium nucleatum presence in the tumor increased according to pathological stage (5.9% [adenoma] to 81.8% [stage III/IV]), while Fn presence in normal mucosa also increased (7.6% [adenoma] to 40.9% [stage III/IV]). The detection rates of Fn on the tumor surface and in deep areas were 45.7% and 32.6%, while that of normal mucosa were 26.1% and 23.9%, respectively. Stage III/IV tumors showed high Fn surface area expression (66.7%). Fn intratumoral heterogeneity (34.8%) was higher than that of KRAS (4.3%; P < 0.001) and BRAF (2.2%; P < 0.001). The Ki-67 index in Fn-positive cases was higher than that in negative cases (93.9% vs 89.0%; P = 0.01). CONCLUSIONS: Fusobacterium nucleatum was strongly present in CRC superficial areas at stage III/IV. The presence of Fn in the deep areas of adjacent normal mucosa also increased. The intratumoral heterogeneity of Fn is important in the use of Fn as a biomarker, as Fn is associated with CRC proliferative capacity.

DOI： 10.1111/jgh.15361

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease. 国際誌

Eriko Yasutomi, Toshihiro Inokuchi, Sakiko Hiraoka, Kensuke Takei, Shoko Igawa, Shumpei Yamamoto, Masayasu Ohmori, Shohei Oka, Yasushi Yamasaki, Hideaki Kinugasa, Masahiro Takahara, Keita Harada, Masaki Furukawa, Kouichi Itoshima, Ken Okada, Fumio Otsuka, Takehiro Tanaka, Toshiharu Mitsuhashi, Jun Kato, Hiroyuki Okada

Scientific reports 11 ( 1 ) 11086 - 11086 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

DOI： 10.1038/s41598-021-90441-x

潰瘍性大腸炎診療におけるバイオマーカーの位置づけを考える新規LRGも含め

安富絵里子, 平岡佐規子, 竹井健介, 井川翔子, 山本峻平, 大森正泰, 岡昌平, 山崎泰史, 井口俊博, 衣笠秀明, 原田馨太, 岡田裕之

日本消化器病学会雑誌 118 ( 臨増総会 ) A360 - A360 2021年3月

Multicenter survey on mesalamine intolerance in patients with ulcerative colitis. 国際誌

Sakiko Hiraoka, Akiko Fujiwara, Tatsuya Toyokawa, Reiji Higashi, Yuki Moritou, Shinjiro Takagi, Kazuhiro Matsueda, Seiyuu Suzuki, Jiro Miyaike, Toshihiro Inokuchi, Masahiro Takahara, Jun Kato, Hiroyuki Okada

Journal of gastroenterology and hepatology 36 ( 1 ) 137 - 143 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Although oral mesalamine is the first-choice drug for treating mild-to-moderate ulcerative colitis (UC), some patients show symptoms of intolerance, including exacerbation of diarrhea and abdominal pain. The present study clarified the current state and clinical courses of patients with mesalamine intolerance. METHODS: Patients who were diagnosed with UC and administered oral mesalamine at eight hospitals in Japan with a follow-up period exceeding 1 year were analyzed. RESULTS: Sixty-seven (11%) of 633 patients showed intolerance to at least one formulation of oral mesalamine. The frequency of mesalamine intolerance has increased in recent years, rising from 5.3% in 2007-2010 to 9.1% in 2011-2013 and 16.2% in 2014-2016. The most common complications were the exacerbation of diarrhea (n = 29), a fever (n = 25), and abdominal pain (n = 22). Readministration of mesalamine/sulfasalazine was attempted in 43 patients, mostly with other types of formulation of mesalamine, and more than half of these patients proved to be tolerant. The risk factors for mesalamine intolerance were female gender (odds ratio [OR] = 1.83; 95% confidence interval [CI], 1.08-3.12), age < 60 years old (OR = 2.82; CI, 1.19-8.33), and pancolitis (OR = 2.09; 95% CI, 1.23-3.60). There were no significant differences in the use of anti-tumor necrosis factor-α agents, colectomy, or steroid-free remission at the last visit between patients with and without mesalamine intolerance. CONCLUSIONS: Mesalamine intolerance is not rare, and its frequency has been increasing recently. The prognosis of patients with mesalamine intolerance did not differ significantly from that of those without intolerance.

DOI： 10.1111/jgh.15138

Liquid biopsy for patients with IBD-associated neoplasia. 国際誌

Hideaki Kinugasa, Sakiko Hiraoka, Kazuhiro Nouso, Shumpei Yamamoto, Mami Hirai, Hiroyuki Terasawa, Eriko Yasutomi, Shohei Oka, Masayasu Ohmori, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Keita Harada, Takehiro Tanaka, Hiroyuki Okada

BMC cancer 20 ( 1 ) 1188 - 1188 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. METHODS: Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. RESULTS: Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. CONCLUSION: Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.

DOI： 10.1186/s12885-020-07699-z

潰瘍性大腸炎における経腹超音波検査の有用性

高原政宏, 平岡佐規子, 大森正泰, 安富絵里子, 岡昌平, 平井麻美, 井口俊博, 山本峻平, 山崎泰史, 衣笠秀明, 原田馨太, 大西秀爾, 岡田裕之

日本消化器病学会雑誌 117 ( 臨増大会 ) A706 - A706 2020年10月

Factors Predicting a Favorable Disease Course Without Anti-TNF Therapy in Crohn's Disease Patients.

Toshihiro Inokuchi, Sakiko Hiraoka, Eriko Yasutomi, Shohei Oka, Yasushi Yamasaki, Hideaki Kinugasa, Masahiro Takahara, Seiji Kawano, Keita Harada, Hiroyuki Okada, Jun Kato

Acta medica Okayama 74 ( 4 ) 265 - 274 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Determining factors that predict a favorable disease course without anti-tumor necrosis factor (TNF) agents would help establish a more cost-effective strategy for Crohn's disease (CD). A retrospective chart review was performed for CD patients with disease durations > 10 years who had not received anti-TNF agents as first-line therapy. Patients were divided into 2 groups: those who received neither anti-TNF agents nor bowel resection (G1), and those who had received an anti-TNF agent and/or bowel resection (G2). The patient backgrounds, therapies and clinical courses were compared between the groups. A total of 62 CD patients met the inclusion criteria (males: 71%; median duration of follow-up: 19 years). Six patients were included in G1; they were significantly less likely to have upper gastrointestinal lesions than G2 (p=0.007). A multivariate analysis revealed that the significant factors for avoidance of bowel resection without anti-TNF treatment were non-stricturing and non-penetrating behaviors, and absence of upper gastrointestinal lesions at the diagnosis (hazard ratios 0.41 and 0.52; p=0.004 and 0.04, respectively). In consideration of the long treatment course of CD, patients with non-stricturing and non-penetrating behaviors and no upper gastrointestinal lesions should not be treated with anti-TNF agents as first-line therapy.

DOI： 10.18926/AMO/60363

Blue laser imaging and linked color imaging improve the color difference value and visibility of colorectal polyps in underwater conditions. 国際誌

Yasushi Yamasaki, Keita Harada, Shumpei Yamamoto, Eriko Yasutomi, Shotaro Okanoue, Mami Hirai, Shohei Oka, Yuka Obayashi, Hiroyuki Sakae, Kenta Hamada, Toshihiro Inokuchi, Hideaki Kinugasa, Yuusaku Sugihara, Masahiro Takahara, Takehiro Tanaka, Sakiko Hiraoka, Yoshiro Kawahara, Hiroyuki Okada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 32 ( 5 ) 791 - 800 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Underwater endoscopic mucosal resection (UEMR) has become widespread for treating colorectal polyps. However, which observational mode is best suited for determining polyp margins underwater remains unclear. To determine the best mode, we analyzed three imaging modes: white light imaging (WLI), blue laser imaging (BLI) and linked color imaging (LCI). METHODS: Images of consecutive colorectal polyps previously examined by these three modes before UEMR were analyzed according to the degree of underwater turbidity (transparent or cloudy). Color differences between the polyps and their surroundings were calculated using the Commission Internationale d'Eclairage Lab color space in which 3-D color parameters were expressed. Eight evaluators, who were blinded to the histology, scored the visibility from one (undetectable) to four (easily detectable) in both underwater conditions. The color differences and visibility scores were compared. RESULTS: Seventy-three polyps were evaluated. Sixty-one polyps (44 adenomatous, 17 serrated) were observed under transparent conditions, and 12 polyps (seven adenomatous, five serrated) were observed under cloudy conditions. Under transparent conditions, color differences for the BLI (8.5) and LCI (7.9) were significantly higher than that of WLI (5.7; P < 0.001). Visibility scores for BLI (3.6) and LCI (3.4) were also higher than that of WLI (3.1; P < 0.0001). Under cloudy conditions, visibility scores for LCI (2.9) and WLI (2.7) were significantly higher than that of BLI (2.2; P < 0.0001 and P = 0.04, respectively). CONCLUSIONS: BLI and LCI were better observational modes in transparent water; however, BLI was unsuitable for cloudy conditions.

DOI： 10.1111/den.13581

Clinical Characteristics and Risk Factors for Rebleeding in Patients with Obscure Gastrointestinal Bleeding.

Yuki Baba, Seiji Kawano, Yoshiyasu Kono, Toshihiro Inokuchi, Hiromitsu Kanzaki, Masaya Iwamuro, Keita Harada, Sakiko Hiraoka, Yoshiro Kawahara, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 59 ( 11 ) 1345 - 1350 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective With the advent of capsule endoscopy (CE) and double-balloon endoscopy (DBE), the diagnosis and treatment of obscure gastrointestinal bleeding (OGIB) have markedly progressed. However, rebleeding sometimes occurs and is difficult to diagnose and treat. The aim of the present study was to investigate the clinical features of OGIB and risk factors for rebleeding in our hospital. Methods A total of 195 patients who underwent CE and/or DBE for OGIB in our hospital from January 2009 to July 2016 were included in the present study. We analyzed 168 cases of small intestinal OGIB, after excluding 27 cases of extra small intestinal bleeding. The clinical characteristics and risk factors related to rebleeding were retrospectively studied. Results Among the 168 patients who were included in the analysis, 95 patients (56.5%) were male. The mean age was 64.5 years (range, 8 to 87 years). Hypertension (31.0%) was the most frequent comorbidity, followed by chronic kidney disease (19.0%). The final diagnoses were ulcerative lesions (n=50, 29.8%), vascular lesions (n=30, 17.9%), tumors (n=7, 4.2%), and diverticula (n=2, 1.2%). The bleeding source was undetermined in the remaining 79 cases (47.0%). Rebleeding was confirmed in 29 cases (17.3%). In a univariate analysis, chronic kidney disease, vascular lesions, and overt previous bleeding were significantly associated with the risk of rebleeding. A multivariate analysis showed that chronic kidney disease, vascular lesion, and overt previous bleeding were significantly associated with the risk of rebleeding. Conclusion Patients with OGIB with overt previous bleeding, vascular lesions, and/or chronic kidney disease had a higher risk of rebleeding.

DOI： 10.2169/internalmedicine.3628-19

A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn's disease.

Shigeki Bamba, Ryosuke Sakemi, Toshimitsu Fujii, Teruyuki Takeda, Shin Fujioka, Kento Takenaka, Hiroki Kitamoto, Shotaro Umezawa, Hirotake Sakuraba, Toshihiro Inokuchi, Norimasa Fukata, Shinta Mizuno, Masaki Yamashita, Shinichiro Shinzaki, Hiroki Tanaka, Hidetoshi Takedatsu, Ryo Ozaki, Kei Moriya, Manabu Ishii, Tetsu Kinjo, Keiji Ozeki, Makoto Ooi, Ryohei Hayashi, Kazuki Kakimoto, Yuichi Shimodate, Kazuya Kitamura, Akihiro Yamada, Akira Sonoda, Yu Nishida, Kyouko Yoshioka, Shinya Ashizuka, Fumiaki Takahashi, Toshio Shimokawa, Taku Kobayashi, Akira Andoh, Toshifumi Hibi

Journal of gastroenterology 55 ( 6 ) 615 - 626 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Small bowel stricture is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD. METHODS: Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available. RESULTS: A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation. CONCLUSIONS: In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD.

DOI： 10.1007/s00535-020-01670-2

Observer agreement for the diagnosis of intestinal acute graft-vs.-host disease based on the presence of villous atrophy in the terminal ileum. 国際誌

Yuusaku Sugihara, Sakiko Hiraoka, Eriko Yasutomi, Shohei Oka, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Yuki Morito, Sakuma Takahashi, Keita Harada, Takehiro Tanaka, Fumio Otsuka, Hiroyuki Okada

Experimental and therapeutic medicine 19 ( 4 ) 3076 - 3080 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Intestinal graft-vs.-host disease (GVHD) is a serious complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Villous atrophy in the terminal ileum is considered a useful diagnostic indicator for GVHD. However, the inter- and intra-observer agreement regarding the ileocolonoscopic findings indicative of acute intestinal GVHD, i.e., villous atrophy in the terminal ileum, are currently insufficient in multiple institutions. Thus, the present study aimed to investigate the incidence of villous atrophy in the terminal ileum to diagnose acute intestinal GVHD and determine the inter- and intra-observer agreement regarding this result for experienced endoscopists from multiple institutions. Consecutive patients who underwent allo-HSCT were referred to our institution between May 2008 and September 2015. A total of 54 patients underwent total ileocolonoscopy after allo-HSCT due to suspected intestinal acute GVHD. Subsequently, three observers from different institutions evaluated the cases for the presence of villous atrophy in the terminal ileum. In this study, the pathology results were a gold standard to evaluate the predictive value of ileocolonoscopy detection. Definitive pathological and non-pathological GVHD was diagnosed in 22 and 32 cases, respectively. The results of examining whether villous atrophy could predict GVHD were as follows. For three observers (A, B and C), the sensitivity of villous atrophy in the terminal ileum was 86.4, 77.3 and 79.2%, respectively, whereas the specificity was 62.5, 62.5 and 86.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of villous atrophy for GVHD were as follows: The PPV of appearance was 61.3, 58.6 and 82.6%, respectively, whereas the NPV was 87.0, 80.0 and 83.9%, respectively. Kappa coefficients for the inter-observer reliability were 0.85, 0.63 and 0.63 for observers A and B, A and C, and B and C, respectively. The intra-observer kappa coefficient was 0.88 for observer A, 0.73 for observer B and 0.75 for observer C. A substantial observer agreement was achieved for the analysis of villous atrophy in the terminal ileum and the agreement for the predictive histological diagnosis was also excellent. Based on the results of the present study, identification of villous atrophy in the terminal ileum was a clinically effective diagnostic parameter, even if different endoscopists were involved in the diagnosis at multiple institutions. The present study was registered as a trial with the University Hospital Medical Information Network (UMIN; registration no. UMIN000025390).

DOI： 10.3892/etm.2020.8538

Switching between Three Types of Mesalazine Formulation and Sulfasalazine in Patients with Active Ulcerative Colitis Who Have Already Received High-Dose Treatment with These Agents. 国際誌

Eriko Yasutomi, Sakiko Hiraoka, Shumpei Yamamoto, Shohei Oka, Mami Hirai, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Keita Harada, Jun Kato, Hiroyuki Okada

Journal of clinical medicine 8 ( 12 ) 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Oral mesalazine and sulfasalazine (SASP) are key drugs for treating ulcerative colitis (UC). The efficacy of switching from one of the several mesalazine formulations to another is largely unknown. This study assessed the efficacy of switching among three types of mesalazine formulation and SASP for UC therapy. METHODS: UC patients receiving high-dose mesalazine/SASP who switched to other formulations due to disease activity were considered eligible. Efficacy was evaluated 2, 6, and 12 months after switching. RESULTS: A total of 106 switches in 88 UC patients were analyzed. The efficacy at 2 months after switching was observed in 23/39 (59%) cases from any mesalazine formulation to SASP, in 18/55 (33%) cases from one mesalazine to another, and in 2/12 (17%) cases from SASP to any mesalazine formulation. Nine of 43 effective cases showed inefficacy or became intolerant post-switching. Delayed efficacy more than two months after switching was observed in four cases. Steroid-free remission was achieved in 42/106 (39%) cases-within 100 days in 35 of these cases (83%). CONCLUSIONS: Switching from mesalazine to SASP was effective in more than half of cases. The efficacy of switching between mesalazine formulations was lower but may be worth attempting in clinical practice from a safety perspective.

DOI： 10.3390/jcm8122109

Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation. 国際誌

Masahiro Takahara, Akinobu Takaki, Sakiko Hiraoka, Takuya Adachi, Yasuyuki Shimomura, Hiroshi Matsushita, Tien Thi Thuy Nguyen, Kazuko Koike, Airi Ikeda, Shiho Takashima, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Yusaku Sugihara, Keita Harada, Shingo Eikawa, Hidetoshi Morita, Heiichiro Udono, Hiroyuki Okada

Scientific reports 9 ( 1 ) 11934 - 11934 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4+CD45RBhigh T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4+ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4+ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4+ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

DOI： 10.1038/s41598-019-48331-w

Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics. 国際誌

Toshihiro Inokuchi, Sakuma Takahashi, Sakiko Hiraoka, Tatsuya Toyokawa, Shinjiro Takagi, Koji Takemoto, Jiro Miyaike, Tsuyoshi Fujimoto, Reiji Higashi, Yuki Morito, Toru Nawa, Seiyuu Suzuki, Mamoru Nishimura, Masafumi Inoue, Jun Kato, Hiroyuki Okada

Journal of gastroenterology and hepatology 34 ( 8 ) 1329 - 1336 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Although previous studies compared the efficacy of infliximab (IFX) versus adalimumab (ADA) as the first-line biologics for Crohn's disease (CD), the difference in long-term prognosis based on which biologic was used first has scarcely been reported. In particular, the clinical courses after loss of response (LOR) of the first-line biologics are largely unknown. METHODS: A multicenter, retrospective study was performed. Disease courses of biologic-naïve CD patients who were started on IFX or ADA treatment were evaluated, even after LOR of the initial biologics. RESULTS: In total, 263 CD patients were eligible for analysis, 183 were treated with IFX first, and 80 were treated with ADA first. The median observation period was 64.2 months. The cumulative steroid-free remission rates and surgery-free rates did not differ significantly between the patients treated with IFX first and those treated with ADA first (log-rank test P = 0.42 and P = 0.74, respectively). In addition, no significant difference was observed in the rate of occurrence of events associated with ineffectiveness (modification of anti-tumor necrosis factor treatment including intensification, switch, discontinuation, or surgery) between the patient groups (log-rank test P = 0.62). The patients treated with IFX first were likely to discontinue the agent due to adverse events, whereas those treated with ADA first were likely to discontinue due to treatment failure or LOR. CONCLUSIONS: No significant difference was observed in the long-term prognosis between biologic-naïve patients with CD who were started treatment with IFX first and ADA first.

DOI： 10.1111/jgh.14624

The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces. 国際誌

Sakiko Hiraoka, Shiho Takashima, Toshihiro Inokuchi, Asuka Nakarai, Masahiro Takahara, Keita Harada, Yasuhiro Seki, Katsunori Watanabe, Jun Kato, Hiroyuki Okada

Intestinal research 17 ( 2 ) 202 - 209 2019年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. METHODS: Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. RESULTS: The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P<0.0001). The values of Fcal for each assay and the FIT all significantly correlated with the MESs (Spearman rank correlation coefficient, Fcal-LATIA: r=0.58, Fcal-ELISA: r=0.55, and FIT: r=0.72). The mucosal healing predictability (determined by an MES of 0 alone) of the Fcal-LATIA, Fcal-ELISA, and FIT-LATIA with the cutoffs determined by receiver operating characteristic curve analysis was 0.79, 0.78, and 0.92 for sensitivity, respectively, and 0.78, 0.69, and 0.73 for specificity, respectively. CONCLUSIONS: The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC.

DOI： 10.5217/ir.2018.00086

Comparison of Two Electrosurgical Modes for Endoscopic Submucosal Dissection of Superficial Colorectal Neoplasms: A Prospective Randomized Study.

Yuusaku Sugihara, Keita Harada, Shohei Oka, Eriko Yasutomi, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Masahiro Takahara, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada

Acta medica Okayama 73 ( 1 ) 81 - 84 2019年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Endoscopic submucosal dissection (ESD) is reportedly one of the standard treatment strategies for large superficial colorectal neoplasms in Japan because of its high en bloc resection rate. A few technical issues regarding ESD should be considered, one of which is the selection of the Endo-cut I mode versus the Swift-coagulation mode as the electrosurgical unit mode setting during submucosal dissection. We seek to determine which of these two modes is more suitable for submucosal dissections of colorectal tumors with regard to procedure time and safety.

DOI： 10.18926/AMO/56463

Feasibility of Underwater Clip Closure for Large Mucosal Defects after Colorectal Endoscopic Submucosal Dissection. 国際誌

Yasushi Yamasaki, Keita Harada, Shohei Oka, Shiho Takashima, Toshihiro Inokuchi, Yuusaku Sugihara, Masahiro Takahara, Sakiko Hiraoka, Hiroyuki Okada

Digestion 99 ( 4 ) 327 - 332 2019年

記述言語：英語

BACKGROUND/AIMS: Clip closure of mucosal defects after colorectal endoscopic submucosal dissection (C-ESD) may decrease the incidence of delayed adverse events. The size of the defect to be closed by conventional clip is limited, however, and we sometimes encounter incomplete closure when the defect is located at the flexure. As, theoretically, underwater clip closure (UCC) could achieve complete closure despite these difficult cases, we investigated its feasibility. METHODS: We retrospectively analyzed 21 patients who underwent UCC after C-ESD. The main outcome was the UCC success rate, defined as complete closure of the defect. Other outcomes were procedure time, number of clips, and the delayed adverse event rate. RESULTS: The median resected specimen size was 31 mm (range 18-47 mm). The UCC success rate was 100%. The median procedure time was only 11 min (range 6-21 min). The median number of clips was 9 (range 5-16). No delayed adverse event occurred. CONCLUSION: It is feasible to use UCC to close large mucosal defects, although further studies are warranted to assess its efficacy.

DOI： 10.1159/000492815

Seven days triple therapy for eradication of Helicobacter pylori does not alter the disease activity of patients with inflammatory bowel disease. 国際誌

Shinichiro Shinzaki, Toshimitsu Fujii, Shigeki Bamba, Maiko Ogawa, Taku Kobayashi, Masahide Oshita, Hiroki Tanaka, Keiji Ozeki, Sakuma Takahashi, Hiroki Kitamoto, Kazuhito Kani, Sohachi Nanjo, Takeshi Sugaya, Yuko Sakakibara, Toshihiro Inokuchi, Kazuki Kakimoto, Akihiro Yamada, Hisae Yasuhara, Yoko Yokoyama, Takuya Yoshino, Akira Matsui, Misaki Nakamura, Taku Tomizawa, Ryosuke Sakemi, Noriko Kamata, Toshifumi Hibi

Intestinal research 16 ( 4 ) 609 - 618 2018年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: The influences of Helicobacter pylori eradication therapy on the disease course of inflammatory bowel disease (IBD) are still unclear. We therefore conducted a multicenter, retrospective cohort study to evaluate the safety of H. pylori eradication therapy for IBD patients. METHODS: IBD patients with H. pylori eradication from 2005 to 2015 (eradication group) and control patients (non-eradication group; 2 paired IBD patients without H. pylori eradication matched with each eradicated patient) were included. IBD exacerbation (increased/additional IBD drug or IBD-associated hospitalization/surgery) and disease improvement based on the physicians' global assessment were investigated at baseline, and at 2 and 6 months after eradication or observation. RESULTS: A total of 429 IBD (378 ulcerative colitis, 51 Crohn's disease) patients, comprising 144 patients in the eradication group and 285 patients in the non-eradication group, were enrolled at 25 institutions. IBD exacerbation was comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76; 95% confidence interval, 0.78-3.92; P=0.170], 11.8% at 6 months [odds ratio, 1.60; 95% confidence interval, 0.81-3.11; P=0.172]). Based on the physicians' global assessment at 2 months, none of the patients in the eradication group improved, whereas 3.2% of the patients in the non-eradication group improved (P=0.019). Multivariate analysis revealed that active disease at baseline, but not H. pylori eradication, was an independent factor for IBD exacerbation during 2 months' observation period. The overall eradication rate was 84.0%-comparable to previous reports in non-IBD patients. CONCLUSIONS: H. pylori eradication therapy does not alter the short-term disease activity of IBD.

DOI： 10.5217/ir.2018.00044

An Elevated Platelet Count Increases the Risk of Relapse in Ulcerative Colitis Patients with Mucosal Healing. 国際誌

Asuka Nakarai, Jun Kato, Sakiko Hiraoka, Shiho Takashima, Toshihiro Inokuchi, Masahiro Takahara, Yuusaku Sugihara, Keita Harada, Hiroyuki Okada

Gut and liver 12 ( 4 ) 420 - 425 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: Although mucosal healing (MH) has been considered a treatment goal for patients with ulcerative colitis (UC), the risk factors predictive of relapse in patients who achieve MH are unknown. Because the platelet count has been shown to be a marker of inflammation in inflammatory bowel diseases, this study aimed to assess whether the platelet count could predict relapse in UC patients with MH. METHODS: A prospective observational study was performed. UC patients with MH were consecutively enrolled in the study and monitored for at least 2 years or until relapse. The correlation between the incidence of relapse and the platelet count at the time of study enrollment was examined. RESULTS: In total, 43 patients were enrolled, and 14 patients (33%) relapsed. The median platelet count at the time of enrollment in the patients who relapsed significantly differed from that in the patients who did not relapse (27.2×10⁴/μL vs 23.8×10⁴/μL, respectively; p=0.016). A platelet count ＞25.0×10⁴/μL was a significant risk factor for relapse based on a multivariate analysis (hazard ratio, 4.85; 95% confidence interval, 1.07 to 25.28), and according to the Kaplan-Meier analysis, this cutoff could identify patients susceptible to relapse (p=0.041, log-rank test). CONCLUSIONS: The platelet count could be used as a predictor of relapse in UC patients with MH.

DOI： 10.5009/gnl17236

Villous atrophy in the terminal ileum is a specific endoscopic finding correlated with histological evidence and poor prognosis in acute graft-versus-host disease after allo-hematopoietic stem cell transplantation. 国際誌

Yuusaku Sugihara, Sakiko Hiraoka, Nobuharu Fujii, Shiho Takashima, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Kenji Kuwaki, Keita Harada, Takehiro Tanaka, Hiroyuki Okada

BMC gastroenterology 18 ( 1 ) 111 - 111 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Endoscopic biopsy can provide a definitive diagnosis, but the optimal endoscopic approach for diagnosis remains uncertain. This study evaluated whether ileocolonoscopic imaging can predict acute GVHD severity after allo-HSCT. METHODS: Consecutive patients who underwent allo-HSCT were referred to our institution, and those diagnosed with acute GVHD by pathology were included in this retrospective study. RESULTS: Fifty-one of 261 patients who underwent ileocolonoscopy were suspected to have acute intestinal GVHD. We performed univariate and multivariate conditional logistic regression with stepwise variable selection; villous atrophy in the terminal ileum remained a statistically significant predictor of GVHD severity (odds ratio, 4.69; 95% confidence interval, 1.07-20.60, P = 0.04). Patients were classified into three groups based on ileal endoscopic findings in the terminal ileum: group S, GVHD with severe villous atrophy; group M, mild atrophy; and group N, no atrophy. Compared with patients in groups M and N, those in group S had significant clinical GVHD at diagnosis (P = 0.03). In group S, three of four, compared with five of 13 patients in groups M and N, required the addition of second-line agents (P = 0.02). CONCLUSIONS: This study showed that severe atrophy of the terminal ileum predicts severe clinical GVHD that is likely to be refractory to steroid treatment. Thus, the severity of terminal ileum atrophy may serve as a tool in predicting clinically severe GVHD. TRIAL REGISTRATION: Trial Registration Number UMIN 000022805 , Registration date July 1, 2016.

DOI： 10.1186/s12876-018-0829-4

A case of small intestinal neuroendocrine carcinoma diagnosed using double-balloon endoscopy with long-term survival.

Seiji Kawano, Yuichi Miyashima, Yoshio Miyabe, Yoshinari Kawai, Toshihiro Murata, Masashi Uda, Toshihiro Inokuchi, Hiroyuki Okada

Clinical journal of gastroenterology 11 ( 3 ) 240 - 244 2018年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Neuroendocrine neoplasms, including neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), are rare epithelial tumors with a predominant neuroendocrine differentiation. Compared with NETs, NECs have been reported to be rarer and have a poorer prognosis. We present a rare case of small bowel NEC diagnosed using double-balloon endoscopy (DBE) and the long-term survival accomplished via intensive therapy. DBE revealed an ulcerative tumor in the deep jejunum, and biopsy specimens showed large and highly dysplastic tumor cells; immuno-histological synaptophysin and chromogranin A tests were positive, and the Ki-67 index was more than 90%. Partial intestinal resection without complete lymph node dissection was performed and, postoperatively, chemotherapy was administered. The patient was observed for 3 years after chemotherapy, and complete remission was maintained.

DOI： 10.1007/s12328-018-0834-8

Ten Initial Cases of Peroral Endoscopic Myotomy for Treatment of Esophageal Motility Disorders at Okayama University Hospital.

Yuusaku Sugihara, Keita Harada, Ryo Kato, Kenji Yamauchi, Shiho Takashima, Daisuke Takei, Yasushi Yamasaki, Toshihiro Inokuchi, Masahiro Takahara, Sakiko Hiraoka, Hiroyuki Okada

Acta medica Okayama 72 ( 2 ) 99 - 104 2018年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Peroral endoscopic myotomy (POEM) for treatment of esophageal motility disorders has recently been reported to be highly effective and less invasive than other treatment. POEM was recently introduced in Okayama University Hospital under the supervision of a physician from a high-volume center. To verify the safety and efficacy of POEM during its introduction in our institution. We examined 10 cases in whom POEM was performed between January 2016 and April 2017. The patients included 7 men and 3 women, with a median age (range) of 49 years (17-74) and median symptom duration of 6 years (1-21). Seven patients had a straight esophagus, and the remaining 3 had a sigmoid esophagus. According to the Chicago classification, 6 patients were diagnosed with type I achalasia, 2 with type II achalasia, and 2 with distal esophagus spasm. Treatment outcomes and adverse events were evaluated. Treatment success was defined as a > 3 decrease in Eckardt score or a score of <3 at the time of discharge. The treatment success rate was 90%, with the average Eckardt score decreasing significantly, from 4.7 to 0.9 (p<0.05). No mucosal perforation, severe infection, mediastinitis, severe bleeding, or gastroesophageal reflux occurred intraoperatively or postoperatively. POEM was introduced to Okayama University Hospital, and the first 10 cases were accomplished safely and effectively under the supervision of an expert physician from a high-volume center.

DOI： 10.18926/AMO/55849

Evaluation of the Upper Gastrointestinal Tract in Ulcerative Colitis Patients.

Ryo Kato, Masaya Iwamuro, Sakiko Hiraoka, Shiho Takashima, Toshihiro Inokuchi, Masahiro Takahara, Yoshitaka Kondo, Takehiro Tanaka, Hiroyuki Okada

Acta medica Okayama 72 ( 2 ) 105 - 113 2018年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

To analyze the clinical characteristics of patients with ulcerative colitis who have upper gastrointestinal lesions, we retrospectively reviewed the data of 216 patients with ulcerative colitis who underwent esophagogastroduodenoscopy at our institute in April 2008-March 2016. We investigated the endoscopic features and compared the clinical characteristics between the patients with and without upper gastrointestinal lesions. Forty-two patients (19.4%) had upper gastrointestinal lesions, including multiple erosions (n=18), bamboo joint-like appearance (n=17), mucosa with white spots (n=4), friable mucosa (n=2), ulcer (n=1), and purulent deposits within the mucosa (n=1) in the stomach and/or duodenum. Compared to the patients without upper gastrointestinal lesions, those with upper gastrointestinal lesions showed significantly more frequent extraintestinal manifestations (19.0% vs. 8.0%, p<0.05) and a significant history of colectomy (33.3% vs. 12.1%, p<0.01). There were no significant differences with regard to the sex ratio, age at esophagogastroduodenoscopy, gastrointestinal symptoms, time since the diagnosis of ulcerative colitis, type of colitis at the initial diagnosis of ulcerative colitis, or gastric atrophy between the groups. In conclusion, gastroduodenal lesions were identified in 19.4% of the patients with ulcerative colitis. Esophagogastroduodenoscopy is particularly recommended for ulcerative colitis patients who show extraintestinal manifestations and for those who have undergone a colectomy.

DOI： 10.18926/AMO/55850

Fecal Immunochemical Test and Fecal Calprotectin Results Show Different Profiles in Disease Monitoring for Ulcerative Colitis. 国際誌

Sakiko Hiraoka, Toshihiro Inokuchi, Asuka Nakarai, Shiho Takashima, Daisuke Takei, Yuusaku Sugihara, Masahiro Takahara, Keita Harada, Hiroyuki Okada, Jun Kato

Gut and liver 12 ( 2 ) 142 - 148 2018年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: Both fecal immunochemical test (FIT) and fecal calprotectin (Fcal) results are useful biomarkers for ulcerative colitis (UC). However, the situations in which each marker should be used are largely unknown. METHODS: A total of 110 colonoscopy intervals of UC patients were assessed, and correlations between changes in colonoscopic findings and changes in the two aforementioned fecal markers were examined. RESULTS: Among patients with mucosal healing (MH) and negative FIT or Fcal results at the initial colonoscopy, FIT and Fcal findings exhibited accuracies of 93% (38/41) and 79% (26/33), respectively, for predicting the results of the subsequent examination. Among the 24 patients who showed endoscopic activity at the precedent colonoscopy and MH at the subsequent examination, positive-to-negative conversion of FIT and Fcal findings at the subsequent examination was observed in 92% (12/13) and 62% (8/13) of patients, respectively. Among the 43 patients who showed endoscopic activity at both the precedent and subsequent examinations, Fcal findings reflected the change in endoscopic activity better than FIT results (r=0.59, p＜0.0001 vs r=0.30, p=0.054). CONCLUSIONS: The FIT is useful for confirming MH and the occurrence of relapse. In contrast, Fcal is useful for monitoring the mucosal status of patients with active inflammation.

DOI： 10.5009/gnl17013

Simultaneous Measurements of Faecal Calprotectin and the Faecal Immunochemical Test in Quiescent Ulcerative Colitis Patients Can Stratify Risk of Relapse. 国際誌

Asuka Nakarai, Sakiko Hiraoka, Sakuma Takahashi, Tomoki Inaba, Reiji Higashi, Motowo Mizuno, Shiho Takashima, Toshihiro Inokuchi, Yuusaku Sugihara, Masahiro Takahara, Keita Harada, Jun Kato, Hiroyuki Okada

Journal of Crohn's & colitis 12 ( 1 ) 71 - 76 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Both faecal calprotectin [Fcal] and the faecal immunochemical test [FIT] are useful to predict clinical relapse of ulcerative colitis [UC]. However, the difference between Fcal and FIT in ability to predict relapse has scarcely been reported. Whether the combined use of these two faecal markers increases the predictability is also unknown. METHODS: UC patients in clinical remission who underwent colonoscopy were enrolled prospectively, and the Fcal and FIT values were examined at enrolment. Their clinical course was observed for 2 years or until relapse. The correlation between the incidence of relapse and the values of the two markers was examined. RESULTS: A total of 113 patients were enrolled, and 48 [42%] relapsed. Fcal ≥ 75 μg/g and FIT ≥ 110 ng/mL were defined as Fcal-positive and FIT-positive, respectively, according to the receiver operating characteristic curves. Both Fcal-positive and FIT-positive statuses were independent predictive factors of clinical relapse (hazard ratio [HR] 2.29; 95% confidence interval [CI], 1.23-4.49; p = 0.0086, and HR 2.91; 95% CI, 1.49-5.50; p = 0.0022, respectively). Categorisation of patients into three groups according to the faecal marker status [FIT-positive, FIT-negative and Fcal-positive, and both negative] can efficiently stratify the risk of relapse with graded increases in risk [FIT-negative and Fcal-positive: HR 2.05; 95% CI, 1.02-4.43; p = 0.0045, and FIT-positive: HR 5.43; 95% CI, 2.57-11.76; p < 0.0001, compared with both negative]. CONCLUSIONS: Fcal vs FIT showed distinct properties regarding the prediction of relapse in UC. A risk assessment using both faecal markers could increase the predictability for relapse.

DOI： 10.1093/ecco-jcc/jjx118

Efficacy of restarting anti-tumor necrosis factor α agents after surgery in patients with Crohn's disease. 国際誌

Sakiko Hiraoka, Shiho Takashima, Yoshitaka Kondo, Toshihiro Inokuchi, Yuusaku Sugihara, Masahiro Takahara, Seiji Kawano, Keita Harada, Jun Kato, Hiroyuki Okada

Intestinal research 16 ( 1 ) 75 - 82 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: The efficacy of anti-tumor necrosis factor α (anti-TNFα) antibodies for postoperative Crohn's disease (CD) in patients who were treated with these agents prior to surgery is largely unknown. METHODS: CD patients who underwent intestinal resection and received anti-TNFα agents after surgery were divided into 2 groups according to the presence or absence of preoperative anti-TNFα treatment: anti-TNFα restart group or anti-TNFα naïve group. Endoscopic recurrence after surgery was examined according to the preoperative conditions, including administration of anti-TNFα agents before surgery. RESULTS: Thirty-six patients received anti-TNFα antibody after surgery: 22 in the anti-TNFα restart group and 14 in the anti-TNFα naïve group. Endoscopic recurrence after surgery was more frequently observed in the anti-TNFα restart group than in the anti-TNFα naïve group (68% vs. 14%, P<0.001). Multivariate analysis revealed the following significant risk factors of endoscopic recurrence after surgery: anti-TNF restart group (odds ratio [OR], 28.10; 95% CI, 3.08-722.00), age at diagnosis <23 years (OR, 24.30; 95% CI, 1.67-1,312.00), serum albumin concentration at surgery <3.3 g/dL (OR, 34.10; 95% CI, 1.72-2,804.00), and presence of inflammation outside of the surgical site (OR, 21.40; 95% CI, 1.02-2,150.00). Treatment intensification for patients with endoscopic recurrence in the anti-TNFα restart group showed limited responses, with only 1 of 12 patients achieving endoscopic remission. CONCLUSIONS: The efficacy of restarting anti-TNFα antibody treatment after surgery was limited, and treatment intensification or a change to different classes of biologics should be considered for those patients.

DOI： 10.5217/ir.2018.16.1.75

パテンシーカプセルが回腸に長期滞留したクローン病の1例

岩室雅也, 高嶋志保, 井口俊博, 高原政宏, 川野誠司, 平岡佐規子, 近藤喜太, 田中健大, 岡田裕之

日本消化器病学会雑誌(Web) 115 ( 2 ) 203 - 210 2018年

Two Cases of Leiomyoma in the Colon Masquerading as Other Types of Colonic Pedunculated Polyps. 国際誌

Ailee Ikeda, Masaya Iwamuro, Takehiro Tanaka, Toshihiro Inokuchi, Asuka Nakarai, Yuusaku Sugihara, Keita Harada, Sakiko Hiraoka, Yoshiro Kawahara, Hiroyuki Okada

Case reports in gastrointestinal medicine 2018 8272313 - 8272313 2018年

記述言語：英語

We describe two cases of leiomyoma in the colon that were diagnosed histologically after endoscopic resection. The first case was a 79-year-old Japanese woman who presented with a pedunculated polyp of 14 mm length at the splenic flexure. Preoperative diagnosis suggested a colonic mucosubmucosal elongated polyp. The second case was a 29-year-old Japanese woman who presented with a pedunculated polyp of 40 mm length at the hepatic flexure and had an ulcer on top of the polyp. Preoperative diagnosis suggested an inflammatory fibroid polyp. A pathological diagnosis of colonic leiomyoma was made after endoscopic resection in both cases. Both tumors were confirmed to originate, not from the proper muscle layer, but from the muscularis mucosae. These cases underscore that although colonic involvement is infrequent, leiomyomas can display pedunculated morphology in the colon rather than the typical gross appearance of gastrointestinal submucosal tumors seen with sessile morphology.

DOI： 10.1155/2018/8272313

Clinical outcome of patients with obscure gastrointestinal bleeding during antithrombotic drug therapy. 国際誌

Yoshiyasu Kono, Seiji Kawano, Yuki Okamoto, Yuka Obayashi, Yuki Baba, Hiroyuki Sakae, Makoto Abe, Tatsuhiro Gotoda, Toshihiro Inokuchi, Hiromitsu Kanzaki, Masaya Iwamuro, Yoshiro Kawahara, Hiroyuki Okada

Therapeutic advances in gastroenterology 11 1756283X17746930 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The clinical outcome of patients with obscure gastrointestinal bleeding (OGIB) during antithrombotic drug therapy has not been fully investigated. METHODS: Patients who underwent video capsule endoscopy (VCE) for the investigation of OGIB at Okayama University Hospital from January 2009 to March 2016 were enrolled. We evaluated the VCE findings, the patterns of OGIB, and the rate of rebleeding within 1 year in antithrombotic drug users and antithrombotic drug nonusers. RESULTS: A total of 181 patients were enrolled. Among the antithrombotic drug users, the rate of VCE positivity in the patients with overt OGIB was significantly higher in comparison with patients with occult OGIB (45% versus 16%, p = 0.014), whereas there was no significant difference among the antithrombotic drug nonusers (27% versus 26%, p = 1.0). Among the antithrombotic drug users, the rate of rebleeding among the VCE-positive patients was significantly higher in comparison with the VCE-negative patients (50% versus 5.9%, p = 0.011). Moreover, among antithrombotic drug users who did not receive therapeutic intervention, the rate of rebleeding among the VCE-positive patients was significantly higher in comparison with the VCE-negative patients (75% versus 6.3%, p = 0.001). However, among the antithrombotic drug nonusers who did not receive therapeutic intervention, the rebleeding rate of the VCE-positive patients was not significantly different from that of the VCE-negative patients (20% versus 9.4%, p = 0.43). CONCLUSION: Therapeutic intervention should be considered for patients with overt OGIB who are VCE positive and who use antithrombotic drugs due to the high risk of rebleeding.

DOI： 10.1177/1756283X17746930

Findings of Retrograde Contrast Study Through Double-balloon Enteroscopy Predict the Risk of Bowel Resections in Patients with Crohn's Disease with Small Bowel Stenosis. 国際誌

Noriko Okazaki, Toshihiro Inokuchi, Sakiko Hiraoka, Masayasu Ohmori, Shiho Takashima, Daisuke Takei, Yuusaku Sugihara, Masahiro Takahara, Keita Harada, Seiji Kawano, Hiroyuki Okada, Jun Kato

Inflammatory bowel diseases 23 ( 12 ) 2097 - 2103 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Patients with Crohn's disease (CD) with small bowel strictures are at risk of surgery. Double-balloon enteroscopy (DBE) can evaluate the status of the small intestine, and retrograde contrast through the scope enables the surgeon to obtain information beyond the reach of the scope. This study aimed to examine whether a retrograde contrast study through DBE could be used as a predictor of subsequent surgery in patients with CD with small intestinal strictures. METHODS: The findings of DBE with retrograde contrast in 48 patients CD with small bowel strictures were examined. RESULTS: Of the 48 patients, 14 (29%) underwent surgery for small intestinal strictures during a median observation period of 2.4 years (interquartile range: 1.4-3.7 yr). According to the results of the multivariate analysis, a maximum length of strictures ≥20 mm and the ratio of the maximum diameter of prestenotic dilations to the diameter of the normal small intestine ≥1.4 were independent risk factors of surgery for small intestinal strictures (risk ratio = 7.6 [95% confidence interval, 1.8-42.0], P = 0.006; and risk ratio = 52.0 [95% confidence interval, 3.5-2485.1], P = 0.002, respectively). The latter predicted subsequent surgery with 92% sensitivity and 88% specificity. Cumulative surgery-free rates were discriminated significantly according to the presence or absence of these 2 risk factors (log-rank test: P < 0.001). CONCLUSIONS: Findings of retrograde contrast through DBE are helpful to predict risk of surgery in patients with CD with small intestinal strictures.

DOI： 10.1097/MIB.0000000000001175

Metachronous Neoplasia and Local Recurrence after Colorectal Endoscopic Submucosal Dissection.

Daisuke Takei, Keita Harada, Shiho Takashima, Toshihiro Inokuchi, Asuka Nakarai, Yusaku Sugihara, Masanobu Takahara, Sakiko Hiraoka, Hiroyuki Okada

Acta medica Okayama 71 ( 6 ) 475 - 483 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Several reports discussed colonoscopic surveillance after polypectomy and endoscopic mucosal resection (EMR) for colorectal polyps, but only a few reports focused on prognostic analyses, and none involved metachronous neoplasia after colorectal endoscopic submucosal dissection (ESD). We conducted the present study to assess the risk of adenoma recurrence requiring endoscopic treatment, and to establish appropriate post-ESD colonoscopic surveillance. We enrolled 116 patients who had undergone colorectal ESD at Okayama University Hospital between February 2008 and July 2014 and had been followed-up >12 months. We retrospectively analyzed clinicopathological features of 101 lesions from 101 patients. Metachronous adenomas were detected in 21 cases (20.8%). We divided the patients into 2 groups according to the occurrence of metachronous adenomas. Our comparison of clinicopathological characteristics between these groups showed that in the metachronous adenomas group the number of synchronous adenomas at index colonoscopy was high and the rate of laterally spreading tumor-nongranular (LST-NG) was higher. A multivariate analysis indicated that the number of synchronous adenomas was significantly associated with metachronous adenomas (HR: 2.54, 95%CI: 1.04-6.52, p<0.05). The colonoscopic surveillance planning after colorectal ESD should be more meticulous for patients with more synchronous adenomas.

DOI： 10.18926/AMO/55584

Two electrosurgical endo-knives for endoscopic submucosal dissection of colorectal superficial neoplasms: a prospective randomized study. 国際誌

Yuusaku Sugihara, Keita Harada, Yoshiro Kawahara, Daisuke Takei, Shiho Takashima, Toshihiro Inokuchi, Asuka Nakarai, Masahiro Takahara, Kenji Kuwaki, Sakiko Hiraoka, Hiroyuki Okada

Endoscopy international open 5 ( 8 ) E729-E735 2017年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND STUDY AIMS: Few studies have directly compared endo-knives for endoscopic submucosal dissection (ESD) in humans. We compared the performances of the Mucosectom2 and SB knife Jr. PATIENTS AND METHODS: Two trainee endoscopists performed ESD of 36 lesions in this prospective, randomized controlled trial. Mucosal incision with a 1.5-mm Dual knife and submucosal dissection using the Mucosectom2 were performed in 1 group. Mucosal incision with a 1.5-mm Dual knife and submucosal dissection with a SB knife Jr. were performed in the other group. The primary outcome was the ESD procedure time. Secondary outcomes were total procedure time, self-completion rates, and adverse events. RESULTS: ESD time in Mucosectom2 patients was not significantly shorter than in SB knife Jr. patients (57 ± 32 min vs. 61 ± 44 min, respectively; P = 0.94). Total procedure time in Mucosectom2 patients was not significantly shorter than in SB knife Jr. patients (81 ± 42 min vs. 82 ± 51 min, respectively; P = 0.85). The trainee self-completion rate was slightly higher in SB knife Jr. patients than in Mucosectom2 patients, although the difference was not significant (94 % vs. 100 %, respectively; P = 0.959). Fewer hemostatic procedures using the Coagrasper were performed in Mucosectom2 patients than in SB knife Jr. patients, although the difference was not significant (0.62 vs. 0.7, respectively; P = 0.432). CONCLUSIONS: Mucosectom2 and SB knife Jr. did not significantly differ in performance for colorectal ESD to safely and reliably enhance ESD. Knife selection is not as important for learning colorectal ESD as patient- and lesion-related factors.

DOI： 10.1055/s-0043-111792

Corrigendum to "Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation". 国際誌

Seiji Kawano, Akinobu Takaki, Masaya Iwamuro, Tetsuya Yasunaka, Yoshiyasu Kono, Kou Miura, Toshihiro Inokuchi, Yoshiro Kawahara, Yuzo Umeda, Takahito Yagi, Hiroyuki Okada

BioMed research international 2017 6418529 - 6418529 2017年

Acute Appendicitis Caused by Previous Endoscopic Submucosal Dissection for an Adenoma Adjacent to the Appendiceal Orifice. 国際誌

Ryo Kato, Keita Harada, Kei Harada, Daisuke Takei, Yuusaku Sugihara, Shiho Takashima, Toshihiro Inokuchi, Masahiro Takahara, Sakiko Hiraoka, Yasushi Omura, Wakako Oda, Hiroyuki Okada

Case reports in gastroenterology 11 ( 2 ) 271 - 276 2017年

記述言語：英語

Endoscopic submucosal dissection (ESD) is a groundbreaking treatment for tumors adjacent to the appendiceal orifice that are difficult to remove by conventional endoscopic mucosal resection, and successful cases are increasingly reported. However, little is known about the subsequent complications, especially long-term complications. A female in her early 70s with a 15-mm cecal tumor adjacent to the appendiceal orifice - discovered incidentally during a screening colonoscopy - underwent hybrid ESD of the lesion. We completely resected the tumor, and she was discharged 5 days later with a pathological diagnosis of high-grade tubular adenoma. Ten months postoperatively, she experienced sudden-onset right lower quadrant pain and was diagnosed with acute appendicitis at another hospital. Due to suspicion that her condition was the result of residual tumor, her surgeon performed an emergency laparoscopic cecectomy. The pathological examination of the resected specimen showed thick scarring adjacent to the appendiceal orifice and no residual tumor. The previous ESD was identified as the cause of the scar, and the scar was the only finding to account for the patient's appendicitis. This case is significant because the patient required additional surgery due to a complication of ESD. Further, it indicates that acute appendicitis may be a late complication of submucosal dissection near the appendiceal orifice. As ESD becomes more widely used, it is likely that more cecal tumors will be treated endoscopically. It is important to be aware of the late complications of ESD for these tumors.

DOI： 10.1159/000475753

Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation. 国際誌

Kawano Seiji, Takaki Akinobu, Iwamuro Masaya, Yasunaka Tetsuya, Kono Yoshiyasu, Miura Kou, Inokuchi Toshihiro, Kawahara Yoshiro, Umeda Yuzo, Yagi Takahito, Okada Hiroyuki

BioMed research international 2017 8193821 - 8193821 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and Aims. Gastrointestinal surveillance is a requirement prior to liver transplantation (LT), but small intestine examination is not generally undertaken. The aim of the present study was to evaluate the safety and efficacy of capsule endoscopy (CE) for patients with end-stage liver disease. Methods. 31 patients who needed LT were enrolled, and 139 patients who underwent CE over the same period of time acted as controls. Results. Frequency of successful achievement of evaluation of the full length of the small bowel, the mean gastric transit time, and the mean small bowel transit time were not significantly different between the two groups. Abnormalities in the small bowel were found in 26 patients. Comparative analysis revealed that history of EV rupture, history of EV treatment, red color sign of EV, and presence of PHG or HCC were significantly associated with patients with >2 two such findings (high score group). Conclusions. Small bowel examination by CE in patients before liver transplantation could be performed safely and is justified by the high rate of abnormal lesions detected particularly in patients with history of EV therapy or bleeding, red color sign, and presence of PHG or HCC. This study was registered in the UMIN Clinical Trial Registry (UMIN 000008672).

DOI： 10.1155/2017/8193821

POEM (Per-Oral Endoscopic Myotomy) を施行した食道アカラシアの1例

杉原雄策, 原田馨太, 加藤諒, 山内健司, 高嶋志保, 竹井大介, 井口俊博, 高原政宏, 川野誠司, 平岡佐規子, 田辺俊介, 野間和宏, 白川靖博, 眞部紀明, 井上晴洋, 岡田裕之

岡山医学会雑誌 129 ( 2 ) 115 - 121 2017年

記述言語：日本語出版者・発行元：岡山医学会

&emsp;Esophageal achalasia is a disorder of the lower esophageal sphincter muscle. Patients present with dysphagia, chest pain, vomiting, and aspiration. Esophageal achalasia had traditionally been treated with esophageal achalasia balloon dilatation and the Heller-Dor method, but in recent years, the use of per-oral endoscopic myotomy (POEM) has increased. Our patient, a 39-yr-old male, began experiencing dysphagia 4 years prior to his referral to our hospital. Based on the results of esophagogastroduodenoscopy, esophageal radiography and high-resolution manometry, we made the diagnosis of esophageal achalasia (Chicago classification type I) . After informed consent from the patient and his family and approval from our hospital's ethics committee were obtained, we performed a POEM. The patient was discharged on the 4th day post-surgery. At the 1-year post-operative examination, no worsening of symptoms and no relapse were observed. POEM is an excellent treatment method for esophageal achalasia from the perspective of therapeutic effect and prevention of invasion. We recommend that it be considered as the first-choice treatment for achalasia. However, accessibility to the procedure itself is limited due to the few adequately trained operators worldwide. POEM should thus be performed by an expert operator at a high-volume center.

DOI： 10.4044/joma.129.115

その他リンク： http://search.jamas.or.jp/link/ui/2017339773

Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse. 国際誌

Asuka Nakarai, Jun Kato, Sakiko Hiraoka, Shiho Takashima, Daisuke Takei, Toshihiro Inokuchi, Yuusaku Sugihara, Masahiro Takahara, Keita Harada, Hiroyuki Okada

World journal of gastroenterology 22 ( 21 ) 5079 - 87 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results. METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results. RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23). CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.

DOI： 10.3748/wjg.v22.i21.5079

Consecutive Measurements by Faecal Immunochemical Test in Quiescent Ulcerative Colitis Patients Can Detect Clinical Relapse. 国際誌

Sakiko Hiraoka, Jun Kato, Asuka Nakarai, Shiho Takashima, Toshihiro Inokuchi, Daisuke Takei, Yuusaku Sugihara, Masahiro Takahara, Keita Harada, Hiroyuki Okada

Journal of Crohn's & colitis 10 ( 6 ) 687 - 94 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: We have reported that results of the quantitative faecal immunochemical test (FIT; haemoglobin concentrations in faeces measured using an antibody for human haemoglobin) effectively reflect the mucosal status of ulcerative colitis (UC). The aim of this study was to evaluate the predictability of flare-up in quiescent UC patients by consecutive FIT evaluation. METHODS: Patients with UC who fulfilled the following criteria by index colonoscopy were enrolled: clinical remission; mucosal healing (Mayo endoscopic subscore 0); and negative FIT (less than 100ng/mL). These patients were followed up prospectively every 1-3 months by monitoring patient symptoms and FIT results between index and subsequent colonoscopies. RESULTS: The intervals between 2 colonoscopies (median 2.51 years) of 83 patients (49 males, median age at onset 34 years, median disease duration 9.74 years) were analysed. None of the 43 (52%) patients who maintained negative FIT throughout the observation period exhibited clinical relapse. On the other hand, 25/40 (63%) patients who showed positive conversion of FIT during the period experienced relapse. The cutoff FIT value of 450ng/mL could predict relapse with 73% positive predictive value and 96% negative predictive value. Moreover, positive conversion of FIT preceded occurrence of symptoms by 1 month or more in nearly one-third of patients with relapse. CONCLUSIONS: Consecutive measurements of FIT in quiescent UC patients who achieved mucosal healing with negative FIT would help identify patients with clinical relapse whose symptoms had not yet presented. Further investigations are required for more precise prediction of relapse with this modality.

DOI： 10.1093/ecco-jcc/jjw025

Fecal Immunochemical Test Versus Fecal Calprotectin for Prediction of Mucosal Healing in Crohn's Disease. 国際誌

Toshihiro Inokuchi, Jun Kato, Sakiko Hiraoka, Shiho Takashima, Asuka Nakarai, Daisuke Takei, Yuusaku Sugihara, Masahiro Takahara, Seiji Kawano, Keita Harada, Hiroyuki Okada

Inflammatory bowel diseases 22 ( 5 ) 1078 - 85 2016年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Mucosal healing (MH) has been proposed as a treatment goal of inflammatory bowel disease patients. We reported recently that not only fecal calprotectin (Fcal) but also the fecal immunochemical test (FIT) can predict MH in ulcerative colitis. However, the predictive power of the fecal markers for MH in Crohn's disease (CD), particularly with small bowel lesions, has not been reported in detail. The aim of this study was to evaluate the predictability of FIT versus Fcal for MH in CD. METHODS: Consecutive CD patients underwent colonoscopy or balloon-assisted enteroscopy according to the disease location. FIT and Fcal were examined using stool samples collected the day before endoscopy. RESULTS: Seventy-one CD patients were analyzed, of whom 42 (59%) underwent balloon-assisted enteroscopy because of the presence of affected lesions in the small intestine. Both the Fcal and the FIT results were significantly correlated with endoscopic activity (r = 0.67 and 0.54, respectively). However, the FIT results did not correlate with the activity in patients with small bowel lesions alone, whereas Fcal did (r = 0.42 versus 0.78). Fcal predicted MH in CD with 87% sensitivity and 71% specificity, whereas the values for FIT were 96% and 48%, respectively. The specificity for MH among patients with small bowel lesions alone was low for FIT (40%) compared with Fcal (80%). CONCLUSIONS: Both FIT and Fcal were correlated with the mucosal status of CD. However, the specificity of FIT was not satisfactory, particularly for small bowel lesions.

DOI： 10.1097/MIB.0000000000000728

Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin? 国際誌

Jun Kato, Sakiko Hiraoka, Asuka Nakarai, Shiho Takashima, Toshihiro Inokuchi, Masao Ichinose

Intestinal research 14 ( 1 ) 5 - 14 2016年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn's disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted.

DOI： 10.5217/ir.2016.14.1.5

A Randomized Trial of Monopolar Soft-mode Coagulation Versus Heater Probe Thermocoagulation for Peptic Ulcer Bleeding. 国際誌

Tomokazu Nunoue, Ryuta Takenaka, Keisuke Hori, Noriko Okazaki, Kenta Hamada, Yuki Baba, Yasushi Yamasaki, Yoshiyasu Kono, Hiroyuki Seki, Toshihiro Inokuchi, Koji Takemoto, Akihiko Taira, Hirofumi Tsugeno, Shigeatsu Fujiki, Yoshiro Kawahara, Hiroyuki Okada

Journal of clinical gastroenterology 49 ( 6 ) 472 - 6 2015年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Endoscopic therapy has been demonstrated to be effective in achieving hemostasis for bleeding peptic ulcers. Thermal coagulation is one of the most commonly used methods, with a high success rate. Recently, endoscopic submucosal dissection for early gastric carcinoma was developed and hemostasis with soft coagulation using hemostatic forceps was introduced. The aim of this study was to compare the hemostatic efficacy of soft coagulation with heater probe thermocoagulation for peptic ulcer bleeding. METHODS: Patients who visited our hospital with hematemesis or melena underwent emergency endoscopy. Inclusion criteria were presentation with an actively bleeding ulcer, a nonbleeding visible vessel, or an adherent clot. Patients were excluded if they were unwilling to give written informed consent or had a bleeding gastric malignancy. Patients were randomized to receive endoscopic hemostasis with soft coagulation (Group S) or heater probe thermocoagulation (Group H). The primary endpoint was the primary hemostasis rate and secondary endpoints were rebleeding rate, complications, and the procedure time. RESULTS: Between May 2010 and February 2012, a total of 111 patients (89 gastric ulcers and 22 duodenal ulcers) were enrolled. Primary hemostasis was achieved in 54 patients (96%) in Group S and 37 (67%) in Group H (P<0.0001). Rebleeding occurred in 7 patients in Group H and none in Group S. Of these 7 patients, urgent surgery was performed in 1. Perforation occurred in 2 patients in Group H, which was managed conservatively. CONCLUSIONS: For patients with gastroduodenal ulcer bleeding, soft coagulation using monopolar hemostatic forceps is more effective than heater probe thermocoagulation for achieving hemostasis.

DOI： 10.1097/MCG.0000000000000190

Evaluation of Mucosal Healing in Ulcerative Colitis by Fecal Calprotectin Vs. Fecal Immunochemical Test. 国際誌

Shiho Takashima, Jun Kato, Sakiko Hiraoka, Asuka Nakarai, Daisuke Takei, Toshihiro Inokuchi, Yuusaku Sugihara, Masahiro Takahara, Keita Harada, Hiroyuki Okada, Takehiro Tanaka, Kazuhide Yamamoto

The American journal of gastroenterology 110 ( 6 ) 873 - 80 2015年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: We previously showed that a quantitative fecal immunochemical test (FIT) can predict mucosal healing (MH) in ulcerative colitis (UC). Fecal calprotectin (Fcal) has also been reported as an important biomarker of UC activity. The aim of this study was to compare the predictive ability of these two fecal markers for MH in UC. METHODS: FIT and Fcal were examined in stool samples from consecutive UC patients who underwent colonoscopy. Mucosal status was assessed via the Mayo endoscopic subscore (MES). RESULTS: In total, 105 colonoscopies in 92 UC patients were evaluated in conjunction with the FIT and Fcal results. Both FIT and Fcal results were significantly correlated with MES (Spearman's rank correlation coefficient: 0.61 and 0.58, respectively). The sensitivity and specificity of the FIT values (<100 ng/ml) for predicting MH (MES 0 alone) were 0.95 and 0.62, respectively, whereas those of Fcal (<250 μg/g) were 0.82 and 0.62, respectively. The sensitivities became similar when MH was defined as MES 0 or 1 (0.86 vs. 0.86). Although the predictability of MH evaluated by the area under the receiver operating characteristics curve was similar for the two fecal markers (FIT 0.83 vs. Fcal 0.82 for MES 0 alone), the FIT results were relatively robust regardless of the cutoff value selected. CONCLUSIONS: Both FIT and Fcal can efficiently predict MH in UC, but FIT appears to be more sensitive than Fcal for predicting MES 0 alone.

DOI： 10.1038/ajg.2015.66

The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. 国際誌

Sakiko Hiraoka, Jun Kato, Yuki Moritou, Daisuke Takei, Toshihiro Inokuchi, Asuka Nakarai, Sakuma Takahashi, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

BMC gastroenterology 15 53 - 53 2015年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Oral tacrolimus therapy is effective for refractory ulcerative colitis (UC), but dose adjustment according to the trough concentrations which varies largely among individuals, is required. This study aimed to identify factors to predict the tacrolimus dose required for achieving the target trough level for remission induction of UC. METHODS: Forty-seven consecutive UC patients who were treated with tacrolimus were retrospectively analyzed. Tacrolimus doses were adjusted every 2 or 3 days to achieve trough concentrations of 10-15 ng/mL. The dose required for reaching the target trough level was analyzed based on disease characteristics, course of trough concentrations, and gene polymorphism related to tacrolimus metabolism. RESULTS: Median daily dose of tacrolimus required for achieving the target trough level was 0.19 (0.07-0.42) mg/kg, and patients were divided into high or low dose group (< 0.2 mg/kg or > 0.2 mg/kg). The value of initial trough concentration/starting dose was higher in the low dose group than in the high dose group (1.35 ng/mL/mg vs. 0.78 ng/mL/mg, p < 0.0001). Although presence of CYP3A5 *1 was more frequently observed in the high dose group, initial trough concentration was the only significant factor for determining requirement of high dose of tacrolimus (OR = 28.0, 95% confidence interval 3.20 - 631). CONCLUSIONS: The most practical predictor of the dose required for achieving the target trough concentration was the trough concentration measured 2 or 3 days after starting tacrolimus therapy. Our findings would make tarcolimus administration for UC safer, easier and more effective.

DOI： 10.1186/s12876-015-0285-3

An effective and safe sedation technique combining target-controlled infusion pump with propofol, intravenous pentazocine, and bispectral index monitoring for peroral double-balloon endoscopy. 国際誌

Seiji Kawano, Hiroyuki Okada, Masaya Iwamuro, Yoshiyasu Kouno, Kou Miura, Toshihiro Inokuchi, Hiromitsu Kanzaki, Keisuke Hori, Keita Harada, Sakiko Hiraoka, Yoshiro Kawahara, Kazuhide Yamamoto

Digestion 91 ( 2 ) 112 - 6 2015年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: Because peroral double-balloon endoscopy (DBE) is a time-consuming, painful procedure, sedation with analgesics, and/or anesthetics is generally required. The aim of this prospective study was to investigate the safety and efficacy of our sedation protocol for peroral DBE, which consisted of target-controlled infusion (TCI) anesthesia with propofol, an intravenous bolus of pentazocine, and bispectral index (BIS) monitoring. METHODS: A total of 34 consecutive patients who underwent DBE by the oral approach were enrolled. Patients were primarily sedated with a continuous infusion of propofol and adjusted in accordance with the BIS levels. The bolus infusion of pentazocine was performed when the propofol infusion was insufficient. The primary outcome measure of this study was to ensure the safety and efficacy of this sedation technique. The secondary purpose was to identify the characteristics of the patient who required the bolus infusion of pentazocine. RESULTS: Five patients (14.7%) required a reduction in the dose of propofol. However, no patient experienced any serious adverse events. All patients (100%) and 80.6% (25/31) of endoscopists answered that the sedation protocol was 'excellent' or 'enough' for peroral DBE. Eleven patients (32.3%) required a bolus injection of pentazocine. Age <60 years and a total procedure time of >70 min were significant risk-factors for pentazocine use. CONCLUSIONS: A combination of propofol via TCI pump, bolus injection of pentazocine as needed, and BIS monitoring was a safe and effective procedure for peroral DBE. Reasonable satisfaction indices were obtained from both patients and endoscopists. Pentazocine was required for young patients and in cases with longer procedure times.

DOI： 10.1159/000369614

Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count. 国際誌

Asuka Nakarai, Jun Kato, Sakiko Hiraoka, Toshihiro Inokuchi, Daisuke Takei, Yuki Moritou, Mitsuhiro Akita, Sakuma Takahashi, Keisuke Hori, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

World journal of gastroenterology 20 ( 48 ) 18367 - 74 2014年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1. METHODS: UC patients with sustained clinical remission of 6 mo or more at the time of colonoscopy were examined for clinical outcomes and the hazard ratios of clinical relapse according to MES. Parameters, including blood tests, to identify predictive factors for MES 0 and slight endoscopic recurrence in clinically stable patients were assessed. Moreover, a receiver operating characteristic curve was generated, and the area under the curve was calculated to indicate the utility of the parameters for the division between complete and partial mucosal healing. All P values were two-sided and considered significant when less than 0.05. RESULTS: A total of 183 patients with clinical remission were examined. Patients with MES 0 (complete mucosal healing: n = 80, 44%) were much less likely to relapse than those with MES 1 (partial mucosal healing: n = 89, 48%) (P < 0.0001, log-rank test), and the hazard ratio of risk of relapse in patients with MES 1 vs MES 0 was 8.17 (95%CI: 4.19-17.96, P < 0.0001). The platelet count (PLT) < 26 × 10(4)/μL was an independent predictive factor for complete mucosal healing (OR = 4.1, 95%CI: 2.15-7.99). Among patients with MES 0 at the initial colonoscopy, patients of whom colonoscopy findings shifted to MES 1 showed significant increases in PLT compared to those who maintained MES 0 (3.8 × 10(4)/μL vs -0.6 × 10(4)/μL, P < 0.0001). CONCLUSION: The relapse rate differed greatly between patients with complete and partial mucosal healing. A shift from complete to partial healing in clinically stable UC patients can be predicted by monitoring PLT.

DOI： 10.3748/wjg.v20.i48.18367

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status. 国際誌

Toshihiro Inokuchi, Jun Kato, Sakiko Hiraoka, Hideyuki Suzuki, Asuka Nakarai, Tomoko Hirakawa, Mitsuhiro Akita, Sakuma Takahashi, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

World journal of gastroenterology 20 ( 2 ) 509 - 17 2014年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: To clarify the impact of cytomegalovirus (CMV) activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis (UC) patients. METHODS: UC patients with flare-up were divided into CMV-positive and -negative groups according to the CMV antigenemia assay. The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir. RESULTS: The median number of days to initial remission was significantly greater for the patients in the CMV-positive group (21 d vs 16 d, P = 0.009). However, the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups. Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group. CONCLUSION: CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.

DOI： 10.3748/wjg.v20.i2.509

Slight increases in the disease activity index and platelet count imply the presence of active intestinal lesions in C-reactive protein-negative Crohn's disease patients.

Asuka Nakarai, Jun Kato, Sakiko Hiraoka, Toshihiro Inokuchi, Daisuke Takei, Yuki Morito, Mitsuhiro Akita, Sakuma Takahashi, Keisuke Hori, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

Internal medicine (Tokyo, Japan) 53 ( 17 ) 1905 - 11 2014年

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Although the serum C-reactive protein (CRP) level may, to some extent, predict the disease activity in patients with Crohn's disease (CD), it is not always elevated during periods of disease activity. This study aimed to identify factors predicting the presence of active intestinal lesions in CD patients without an elevated CRP level. METHODS: CD patients in whom the presence or absence of active intestinal lesions was evaluated using endoscopic and/or radiologic modalities were divided into two groups based on a negative (<3 mg/L) or positive (≥3 mg/L) CRP level. The correlations between the presence of active intestinal lesions and various clinical variables, including the Crohn's Disease Activity Index (CDAI), leukocyte and platelet counts and hemoglobin, serum albumin and CRP levels, were determined in the CRP-negative patients. RESULTS: Of the 128 patients examined, 70 had a negative CRP status, approximately half of whom had active intestinal lesions. The multivariate analysis revealed a CDAI of >100 and platelet count of >33×10(4)/μL to be significant predictive factors for the presence of active lesions in the CRP-negative patients [CDAI >100, odds ratio (OR) =5.55; 95% confidence interval (CI), 1.80-18.74, platelet count >33×10(4)/μL, OR =5.94; 95% CI, 1.34-28.87]. The sensitivity of fulfillment of either criterion for the presence of active intestinal lesions was 83%, while the specificity of fulfillment of both criteria was 94%. CONCLUSION: A relatively low CDAI and platelet count were identified as predictive markers of the presence of active intestinal lesions in CRP-negative CD patients. These results suggest that symptoms and laboratory data should be evaluated very carefully in such patients.

Endoscopic submucosal dissection for a superficial esophageal squamous cell carcinoma within the parabronchial diverticula. 国際誌

Tatsuhiro Gotoda, Ryuta Takenaka, Toshihiro Inokuchi, Shigeatsu Fujiki

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 25 ( 1 ) 91 - 2 2013年1月

Peppermint oil solution is useful as an antispasmodic drug for esophagogastroduodenoscopy, especially for elderly patients. 国際誌

Atsushi Imagawa, Hidenori Hata, Morihito Nakatsu, Yasunari Yoshida, Keiko Takeuchi, Toshihiro Inokuchi, Takayuki Imada, Yoshiyasu Kohno, Masahiro Takahara, Kazuyuki Matsumoto, Hirokazu Miyatake, Satoru Yagi, Masaharu Ando, Mamoru Hirohata, Shigeatsu Fujiki, Ryuta Takenaka

Digestive diseases and sciences 57 ( 9 ) 2379 - 84 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Although hyoscine butyl bromide (HB) and glucagon (GL) are often used as antispasmodic drugs during esophagogastroduodenoscopy (EGD), these agents may cause adverse effects. Recently, it was reported that peppermint oil solution (PO) was very effective and had few side effects. AIM: We clarified the efficacy and usefulness of PO as an antispasmodic during upper endoscopy, especially for elderly patients. METHODS: This study was a non-randomized prospective study. The antispasmodic score (1-5, where 5 represents no spasm) was defined according to the degree of spasms of the antrum and difficulty of biopsy. We compared the antispasmodic scores between non-elderly patients (younger than 70) and elderly patients (70 years old or older) according to the antispasmodic agent. RESULTS: A total of 8,269 (Group PO: HB: GL: NO (no antispasmodic) = 1,893: 6,063: 157: 156) EGD procedures were performed. There was no significant difference in the antispasmodic score between Group PO (mean score ± standard deviation: 4.025 ± 0.925) and Group HB (4.063 ± 0.887). Among the non-elderly patients, those in Group PO (n = 599, 3.923 ± 0.935) had a worse antispasmodic score than those in Group HB (n = 4,583, 4.062 ± 0.876, P < 0.001). However, among the elderly patients, those in Group PO (n = 1,294, 4.073 ± 0.917) had similar scores to those in Group HB (n = 1,480, 4.064 ± 0.921, P = 0.83), and significantly better scores than those in Group GL (n = 69, 3.797 ± 0.933, P < 0.05). CONCLUSION: Peppermint oil was useful as an antispasmodic during EGD, especially for elderly patients.

DOI： 10.1007/s10620-012-2194-4

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